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    Clinical Trial Results:
    A Phase 2 Study to Evaluate Safety and Anti-tumor Activity of Avelumab in Combination With Talazoparib in Subjects With BRCA or ATM Mutant Tumors

    Summary
    EudraCT number
    2018-000345-39
    Trial protocol
    GB   NL   FR   BE   DK   ES   IT  
    Global end of trial date
    03 Feb 2023

    Results information
    Results version number
    v1(current)
    This version publication date
    16 Sep 2023
    First version publication date
    16 Sep 2023
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    B9991032
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT03565991
    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
    03 Feb 2023
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    03 Feb 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of the study was to evaluate objective response rate (ORR) of avelumab in combination with talazoparib, in subjects with locally advanced or metastatic solid tumors harboring BRCA1, BRCA2 or ATM defect.
    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
    18 Jun 2018
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety, Efficacy
    Long term follow-up duration
    52 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Belgium: 9
    Country: Number of subjects enrolled
    Denmark: 3
    Country: Number of subjects enrolled
    France: 5
    Country: Number of subjects enrolled
    Italy: 31
    Country: Number of subjects enrolled
    Japan: 9
    Country: Number of subjects enrolled
    Netherlands: 3
    Country: Number of subjects enrolled
    Spain: 10
    Country: Number of subjects enrolled
    United Kingdom: 4
    Country: Number of subjects enrolled
    United States: 126
    Worldwide total number of subjects
    200
    EEA total number of subjects
    61
    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)
    135
    From 65 to 84 years
    63
    85 years and over
    2

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    A total of 270 subjects were screened for this study, 202 subjects were enrolled and assigned to study treatment but 2 subjects never started the treatment. In total 200 subjects were treated (159 in Cohort 1 and 41 in Cohort 2).

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Cohort 1 (BReast CAncer Gene [BRCA] 1/2 defect)
    Arm description
    Subjects with locally advanced or metastatic solid tumors with one or more defects in the BRCA1 or BRCA2 genes were enrolled in Cohort 1. Talazoparib was self-administered orally at a starting dose of 1 mg Once Daily (QD) for subjects with normal renal function or mild renal impairment until End of Treatment. Subjects with moderate renal impairment received starting dose of 0.75 mg QD. Avelumab was administered as a 1-hour Intravenous (IV) infusion Every 2 Weeks (Q2W) on Days 1 and 15 of each 28-day cycle at a dose of 800 mg after administration of talazoparib and the premedication.
    Arm type
    Experimental

    Investigational medicinal product name
    Avelumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Avelumab was administered as a 1-hour IV infusion Q2W at a dose of 800 mg.

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Talazoparib was administered orally at 1 mg QD for subjects with normal renal function or mild renal impairment until End of Treatment. Talazoparib was administered orally at 0.75 mg QD for subjects with moderate renal impairment.

    Arm title
    Cohort 2 (Ataxia Telangiectasia Mutated [ATM] defect)
    Arm description
    Subjects with locally advanced or metastatic solid tumors with one or more defects in the ATM gene without concurrent BRCA1/2 defect were enrolled in Cohort 2. Talazoparib was self-administered orally at a starting dose of 1 mg QD for subjects with normal renal function or mild renal impairment until End of Treatment. Subjects with moderate renal impairment received starting dose of 0.75 mg QD. Avelumab was administered as a 1-hour IV infusion Q2W on Days 1 and 15 of each 28-day cycle at a dose of 800 mg after administration of talazoparib and the premedication.
    Arm type
    Experimental

    Investigational medicinal product name
    Avelumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Avelumab was administered as a 1-hour IV infusion Q2W at a dose of 800 mg.

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Talazoparib was administered orally at 1 mg QD for subjects with normal renal function or mild renal impairment until End of Treatment. Talazoparib was administered orally at 0.75 mg QD for subjects with moderate renal impairment.

    Number of subjects in period 1
    Cohort 1 (BReast CAncer Gene [BRCA] 1/2 defect) Cohort 2 (Ataxia Telangiectasia Mutated [ATM] defect)
    Started
    159
    41
    Completed
    1
    0
    Not completed
    158
    41
         Adverse event, serious fatal
    1
    -
         Adverse event, not serious
    4
    1
         Consent withdrawn by subject
    2
    6
         Global deterioration of health status
    14
    4
         Death
    3
    -
         Adverse event, serious non-fatal
    2
    1
         Unspecified
    11
    -
         Progressive disease
    121
    29

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Cohort 1 (BReast CAncer Gene [BRCA] 1/2 defect)
    Reporting group description
    Subjects with locally advanced or metastatic solid tumors with one or more defects in the BRCA1 or BRCA2 genes were enrolled in Cohort 1. Talazoparib was self-administered orally at a starting dose of 1 mg Once Daily (QD) for subjects with normal renal function or mild renal impairment until End of Treatment. Subjects with moderate renal impairment received starting dose of 0.75 mg QD. Avelumab was administered as a 1-hour Intravenous (IV) infusion Every 2 Weeks (Q2W) on Days 1 and 15 of each 28-day cycle at a dose of 800 mg after administration of talazoparib and the premedication.

    Reporting group title
    Cohort 2 (Ataxia Telangiectasia Mutated [ATM] defect)
    Reporting group description
    Subjects with locally advanced or metastatic solid tumors with one or more defects in the ATM gene without concurrent BRCA1/2 defect were enrolled in Cohort 2. Talazoparib was self-administered orally at a starting dose of 1 mg QD for subjects with normal renal function or mild renal impairment until End of Treatment. Subjects with moderate renal impairment received starting dose of 0.75 mg QD. Avelumab was administered as a 1-hour IV infusion Q2W on Days 1 and 15 of each 28-day cycle at a dose of 800 mg after administration of talazoparib and the premedication.

    Reporting group values
    Cohort 1 (BReast CAncer Gene [BRCA] 1/2 defect) Cohort 2 (Ataxia Telangiectasia Mutated [ATM] defect) Total
    Number of subjects
    159 41 200
    Age Categorical
    Units: Subjects
        < 65 years
    110 25 135
        65 - <75 years
    34 11 45
        75 - <85 years
    15 3 18
        >=85 years
    0 2 2
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    57.35 ± 12.88 61.76 ± 12.47 -
    Sex: Female, Male
    Units: Subjects
        Female
    108 24 132
        Male
    51 17 68
    Race/Ethnicity, Customized
    Units: Subjects
        Black or African American
    8 3 11
        American Indian or Alaska Native
    1 0 1
        Asian
    15 0 15
        White
    117 37 154
        Not reported
    18 1 19
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    11 2 13
        Not Hispanic or Latino
    131 39 170
        Unknown or Not Reported
    17 0 17
    Subject analysis sets

    Subject analysis set title
    Avelumab 800 mg Intravenous (IV) Q2W plus talazoparib
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Talazoparib was self-administered orally QD at a dose of 1 mg QD for subjects with normal renal function or mild renal impairment until End of Treatment. Subjects with moderate renal impairment received 0.75 mg QD. Avelumab was administered as a 1-hour IV infusion Q2W on Days 1 and 15 of each 28-day cycle at a dose of 800 mg after administration of talazoparib and the premedication.

    Subject analysis sets values
    Avelumab 800 mg Intravenous (IV) Q2W plus talazoparib
    Number of subjects
    200
    Age Categorical
    Units: Subjects
        < 65 years
    135
        65 - <75 years
    45
        75 - <85 years
    18
        >=85 years
    2
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    58.25 ± 12.89
    Sex: Female, Male
    Units: Subjects
        Female
    132
        Male
    68
    Race/Ethnicity, Customized
    Units: Subjects
        Black or African American
    11
        American Indian or Alaska Native
    1
        Asian
    15
        White
    154
        Not reported
    19
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    13
        Not Hispanic or Latino
    170
        Unknown or Not Reported
    17

    End points

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    End points reporting groups
    Reporting group title
    Cohort 1 (BReast CAncer Gene [BRCA] 1/2 defect)
    Reporting group description
    Subjects with locally advanced or metastatic solid tumors with one or more defects in the BRCA1 or BRCA2 genes were enrolled in Cohort 1. Talazoparib was self-administered orally at a starting dose of 1 mg Once Daily (QD) for subjects with normal renal function or mild renal impairment until End of Treatment. Subjects with moderate renal impairment received starting dose of 0.75 mg QD. Avelumab was administered as a 1-hour Intravenous (IV) infusion Every 2 Weeks (Q2W) on Days 1 and 15 of each 28-day cycle at a dose of 800 mg after administration of talazoparib and the premedication.

    Reporting group title
    Cohort 2 (Ataxia Telangiectasia Mutated [ATM] defect)
    Reporting group description
    Subjects with locally advanced or metastatic solid tumors with one or more defects in the ATM gene without concurrent BRCA1/2 defect were enrolled in Cohort 2. Talazoparib was self-administered orally at a starting dose of 1 mg QD for subjects with normal renal function or mild renal impairment until End of Treatment. Subjects with moderate renal impairment received starting dose of 0.75 mg QD. Avelumab was administered as a 1-hour IV infusion Q2W on Days 1 and 15 of each 28-day cycle at a dose of 800 mg after administration of talazoparib and the premedication.

    Subject analysis set title
    Avelumab 800 mg Intravenous (IV) Q2W plus talazoparib
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Talazoparib was self-administered orally QD at a dose of 1 mg QD for subjects with normal renal function or mild renal impairment until End of Treatment. Subjects with moderate renal impairment received 0.75 mg QD. Avelumab was administered as a 1-hour IV infusion Q2W on Days 1 and 15 of each 28-day cycle at a dose of 800 mg after administration of talazoparib and the premedication.

    Primary: Percentage of Subjects With Confirmed Objective Response (OR) as Assessed by Blinded Independent Central Review (BICR)

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    End point title
    Percentage of Subjects With Confirmed Objective Response (OR) as Assessed by Blinded Independent Central Review (BICR) [1]
    End point description
    For subjects with solid tumors except metastatic Castration Resistant Prostate Cancer (mCRPC),OR was defined as a complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors version 1.1(RECIST v1.1),both confirmed by repeat assessments performed >=4 weeks after the criteria for response were first met.For subjects with mCRPC, OR was defined as the percentage of subjects with a best overall soft tissue response of CR or PR per RECIST v1.1 with no evidence of confirmed bone disease progression per Prostate Cancer Working Group3(PCWG3) criteria.CR was defined as complete disappearance of all target&non-target lesions with the exception of nodal disease.PR was defined as >=30% decrease under baseline of the sum of diameters of all target measurable lesions.Non-target PR lesions must be non-Progressive Disease (PD),which was unequivocal progression of pre-existing lesions.The analysis set included all enrolled subjects with >=1 dose of study treatment.
    End point type
    Primary
    End point timeframe
    From the first dose of study treatment until the date of first documented disease progression or date of death from any cause, whichever came first, assessed up to approximately 24 months
    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
    Cohort 1 (BReast CAncer Gene [BRCA] 1/2 defect) Cohort 2 (Ataxia Telangiectasia Mutated [ATM] defect)
    Number of subjects analysed
    159
    41
    Units: Percentage of subjects
        number (confidence interval 95%)
    27.7 (20.9 to 35.3)
    7.3 (1.5 to 19.9)
    No statistical analyses for this end point

    Secondary: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs)

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    End point title
    Number of Subjects With Treatment-Emergent Adverse Events (TEAEs)
    End point description
    An adverse event (AE) was any untoward medical occurrence in a clinical investigation where subjects administered a product. TEAEs were those events with onset dates occurring during the on-treatment period. A Serious Adverse Event (SAE) was any untoward medical occurrence at any dose that: resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or resulted in congenital anomaly/birth defect. A treatment-related AE was any untoward medical occurrence attributed to the study drug in a subject who received study drug. TEAEs were graded using National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) v4.03 as Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death related to AE. The safety analysis set included all enrolled subjects who received at least 1 dose of study treatment.
    End point type
    Secondary
    End point timeframe
    From baseline up to 30 days after last dose of study treatment, maximum up to 4.3 years approximately
    End point values
    Cohort 1 (BReast CAncer Gene [BRCA] 1/2 defect) Cohort 2 (Ataxia Telangiectasia Mutated [ATM] defect)
    Number of subjects analysed
    159
    41
    Units: Subjects
        TEAEs
    156
    40
        treatment-related TEAEs
    148
    34
        grade >=3 TEAEs
    114
    22
        grade >=3 treatment-related TEAEs
    85
    17
        SAEs
    50
    7
        treatment-related SAEs
    12
    4
        TEAEs leading to all study drugs' discontinuation
    5
    2
        treatment-related TEAEs (study drugs discontinue)
    0
    1
        TEAEs leading to death
    14
    2
        treatment-related TEAEs leading to death
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period

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    End point title
    Number of Subjects With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period
    End point description
    The laboratory results were graded according to the CTCAE v4.03. The number and percentage of subjects with newly occurring or worsening hematology abnormalities to Grade>=1 during the on-treatment period were summarized. Per NCI CTCAE toxicity grading v4.03, Grade 1(G1) = mild; Grade 2(G2) = moderate; Grade 3(G3) = severe; Grade 4(G4) = life-threatening; Grade 5(G5) = death related to AE. On-treatment period was defined as the time from the first dose of study treatment through minimum (30 days + last dose of study treatment, start day of new anti-cancer drug therapy -1 day). The safety analysis set included all enrolled subjects who received at least 1 dose of study treatment. Abbreviations: APTTP=activated partial thromboplastin time prolonged; HI=hemoglobin increased; INR=International Normalized Ratio; LCD=lymphocyte count decreased; LCI=lymphocyte count increased; NCD=neutrophil count decreased; N/W=new or worsened; PCD=platelet count decreased; WBCD=white blood cell decreased.
    End point type
    Secondary
    End point timeframe
    From baseline up to 30 days after last dose of study treatment, maximum up to 4.3 years approximately
    End point values
    Cohort 1 (BReast CAncer Gene [BRCA] 1/2 defect) Cohort 2 (Ataxia Telangiectasia Mutated [ATM] defect)
    Number of subjects analysed
    159 [2]
    41 [3]
    Units: Subjects
        N/W to G1 (Parameter: APTTP) (n=5,1)
    0
    0
        N/W to G2 (Parameter: APTTP) (n=5,1)
    0
    0
        N/W to G3 (Parameter: APTTP) (n=5,1)
    0
    0
        N/W to G4 (Parameter: APTTP) (n=5,1)
    0
    0
        N/W to G1 (Parameter: anemia) (n=151,40)
    27
    9
        N/W to G2 (Parameter: anemia) (n=151,40)
    33
    6
        N/W to G3 (Parameter: anemia) (n=151,40)
    61
    12
        N/W to G4 (Parameter: anemia) (n=151,40)
    0
    0
        N/W to G1 (Parameter: HI) (n=157,41)
    1
    0
        N/W to G2 (Parameter: HI) (n=157,41)
    0
    0
        N/W to G3 (Parameter: HI) (n=157,41)
    0
    0
        N/W to G4 (Parameter: HI) (n=157,41)
    0
    0
        N/W to G1 (Parameter: INR) (n=6,0)
    1
    0
        N/W to G2 (Parameter: INR) (n=6,0)
    0
    0
        N/W to G3 (Parameter: INR) (n=6,0)
    0
    0
        N/W to G4 (Parameter: INR) (n=6,0)
    0
    0
        N/W to G1 (Parameter: LCD) (n=154,40)
    15
    6
        N/W to G2 (Parameter: LCD) (n=154,40)
    58
    15
        N/W to G3 (Parameter: LCD) (n=154,40)
    34
    7
        N/W to G4 (Parameter: LCD) (n=154,40)
    3
    0
        N/W to G1 (Parameter: LCI) (n=156,41)
    0
    0
        N/W to G2 (Parameter: LCI) (n=156,41)
    3
    0
        N/W to G3 (Parameter: LCI) (n=156,41)
    1
    0
        N/W to G4 (Parameter: LCI) (n=156,41)
    0
    0
        N/W to G1 (Parameter: NCD) (n=154,40)
    15
    2
        N/W to G2 (Parameter: NCD) (n=154,40)
    42
    8
        N/W to G3 (Parameter: NCD) (n=154,40)
    16
    4
        N/W to G4 (Parameter: NCD) (n=154,40)
    3
    1
        N/W to G1 (Parameter: PCD) (n=152,41)
    59
    16
        N/W to G2 (Parameter: PCD) (n=152,41)
    16
    3
        N/W to G3 (Parameter: PCD) (n=152,41)
    14
    4
        N/W to G4 (Parameter: PCD) (n=152,41)
    11
    1
        N/W to G1 (Parameter: WBCD) (n=156,41)
    45
    14
        N/W to G2 (Parameter: WBCD) (n=156,41)
    52
    11
        N/W to G3 (Parameter: WBCD) (n=156,41)
    15
    5
        N/W to G4 (Parameter: WBCD) (n=156,41)
    2
    0
    Notes
    [2] - Subjects with available data (n=X, X in category titles) were analyzed.
    [3] - Subjects with available data (n=X, X in category titles) were analyzed.
    No statistical analyses for this end point

    Secondary: Number of Subjects With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period

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    End point title
    Number of Subjects With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period
    End point description
    The laboratory results were graded according to the CTCAE v4.03. The number and percentage of subjects with newly occurring or worsening chemistry abnormalities to Grade >=1 during the on-treatment period were summarized. As per NCI CTCAE toxicity grading v4.03, Grade1(G1)=mild; Grade2(G2)=moderate; Grade3(G3)=severe; Grade4(G4)=life-threatening; Grade5(G5)=death related to AE. On-treatment period was defined as the time from the first dose of study treatment through minimum (30days + last dose of study treatment, start day of new anti-cancer drug therapy -1day). The safety analysis set included all enrolled subjects who received at least 1 dose of study treatment. Abbreviations: ALTI=alanine aminotransferase increased; ALPI=alkaline phosphatase increased; ASTI=aspartate aminotransferase increased; BBI=blood bilirubin increased; CPKI=creatine phosphokinase increased; CI=creatinine increased; GGTI=gamma glutamyl transferase increased; LI=lipase increased; SAI=serum amylase increased.
    End point type
    Secondary
    End point timeframe
    From baseline up to 30 days after last dose of study treatment, maximum up to 4.3 years approximately
    End point values
    Cohort 1 (BReast CAncer Gene [BRCA] 1/2 defect) Cohort 2 (Ataxia Telangiectasia Mutated [ATM] defect)
    Number of subjects analysed
    159 [4]
    41 [5]
    Units: Subjects
        N/W to G1 (Parameter: ALTI) (n=152,41)
    30
    10
        N/W to G2 (Parameter: ALTI) (n=152,41)
    6
    0
        N/W to G3 (Parameter: ALTI) (n=152,41)
    3
    3
        N/W to G4 (Parameter: ALTI) (n=152,41)
    1
    0
        N/W to G1 (Parameter: ALPI) (n=153,41)
    25
    12
        N/W to G2 (Parameter: ALPI) (n=153,41)
    21
    5
        N/W to G3 (Parameter: ALPI) (n=153,41)
    7
    1
        N/W to G4 (Parameter: ALPI) (n=153,41)
    1
    0
        N/W to G1 (Parameter: ASTI) (n=150,40)
    35
    5
        N/W to G2 (Parameter: ASTI) (n=150,40)
    13
    2
        N/W to G3 (Parameter: ASTI) (n=150,40)
    2
    4
        N/W to G4 (Parameter: ASTI) (n=150,40)
    1
    0
        N/W to G1 (Parameter: BBI) (n=154,40)
    7
    2
        N/W to G2 (Parameter: BBI) (n=154,40)
    7
    2
        N/W to G3 (Parameter: BBI) (n=154,40)
    2
    1
        N/W to G4 (Parameter: BBI) (n=154,40)
    0
    0
        N/W to G1 (Parameter: CPKI) (n=151,41)
    22
    3
        N/W to G2 (Parameter: CPKI) (n=151,41)
    8
    1
        N/W to G3 (Parameter: CPKI) (n=151,41)
    2
    3
        N/W to G4 (Parameter: CPKI) (n=151,41)
    0
    1
        N/W to G1 (Parameter: CI) (n=153,40)
    87
    24
        N/W to G2 (Parameter: CI) (n=153,40)
    12
    4
        N/W to G3 (Parameter: CI) (n=153,40)
    1
    0
        N/W to G4 (Parameter: CI) (n=153,40)
    1
    0
        N/W to G1 (Parameter: GGTI) (n=147,40)
    23
    8
        N/W to G2 (Parameter: GGTI) (n=147,40)
    16
    5
        N/W to G3 (Parameter: GGTI) (n=147,40)
    26
    7
        N/W to G4 (Parameter: GGTI) (n=147,40)
    1
    1
        N/W to G1 (Parameter: hypercalcemia) (n=156,41)
    11
    4
        N/W to G2 (Parameter: hypercalcemia) (n=156,41)
    0
    0
        N/W to G3 (Parameter: hypercalcemia) (n=156,41)
    1
    0
        N/W to G4 (Parameter: hypercalcemia) (n=156,41)
    0
    0
        N/W to G1 (Parameter: hyperglycemia) (n=155,41)
    23
    5
        N/W to G2 (Parameter: hyperglycemia) (n=155,41)
    2
    0
        N/W to G3 (Parameter: hyperglycemia) (n=155,41)
    3
    2
        N/W to G4 (Parameter: hyperglycemia) (n=155,41)
    1
    0
        N/W to G1 (Parameter: hyperkalemia) (n=156,40)
    13
    3
        N/W to G2 (Parameter: hyperkalemia) (n=156,40)
    6
    0
        N/W to G3 (Parameter: hyperkalemia) (n=156,40)
    1
    0
        N/W to G4 (Parameter: hyperkalemia) (n=156,40)
    1
    0
        N/W to G1 (Parameter: hypermagnesemia) (n=155,41)
    9
    4
        N/W to G2 (Parameter: hypermagnesemia) (n=155,41)
    0
    0
        N/W to G3 (Parameter: hypermagnesemia) (n=155,41)
    3
    0
        N/W to G4 (Parameter: hypermagnesemia) (n=155,41)
    0
    0
        N/W to G1 (Parameter: hypernatremia) (n=156,41)
    8
    1
        N/W to G2 (Parameter: hypernatremia) (n=156,41)
    0
    0
        N/W to G3 (Parameter: hypernatremia) (n=156,41)
    0
    0
        N/W to G4 (Parameter: hypernatremia) (n=156,41)
    0
    0
        N/W to G1 (Parameter: hypoalbuminemia) (n=150,39)
    21
    6
        N/W to G2 (Parameter: hypoalbuminemia) (n=150,39)
    10
    2
        N/W to G3 (Parameter: hypoalbuminemia) (n=150,39)
    2
    1
        N/W to G4 (Parameter: hypoalbuminemia) (n=150,39)
    0
    0
        N/W to G1 (Parameter: hypocalcemia) (n=153,41)
    27
    2
        N/W to G2 (Parameter: hypocalcemia) (n=153,41)
    6
    1
        N/W to G3 (Parameter: hypocalcemia) (n=153,41)
    3
    0
        N/W to G4 (Parameter: hypocalcemia) (n=153,41)
    0
    0
        N/W to G1 (Parameter: hypoglycemia) (n=155,41)
    10
    4
        N/W to G2 (Parameter: hypoglycemia) (n=155,41)
    1
    0
        N/W to G3 (Parameter: hypoglycemia) (n=155,41)
    0
    0
        N/W to G4 (Parameter: hypoglycemia) (n=155,41)
    0
    0
        N/W to G1 (Parameter: hypokalemia) (n=155,41)
    0
    0
        N/W to G2 (Parameter: hypokalemia) (n=155,41)
    24
    8
        N/W to G3 (Parameter: hypokalemia) (n=155,41)
    4
    1
        N/W to G4 (Parameter: hypokalemia) (n=155,41)
    0
    0
        N/W to G1 (Parameter: hypomagnesemia) (n=156,41)
    24
    5
        N/W to G2 (Parameter: hypomagnesemia) (n=156,41)
    2
    0
        N/W to G3 (Parameter: hypomagnesemia) (n=156,41)
    1
    0
        N/W to G4 (Parameter: hypomagnesemia) (n=156,41)
    1
    0
        N/W to G1 (Parameter: hyponatremia) (n=153,40)
    29
    10
        N/W to G2 (Parameter: hyponatremia) (n=153,40)
    0
    0
        N/W to G3 (Parameter: hyponatremia) (n=153,40)
    11
    2
        N/W to G4 (Parameter: hyponatremia) (n=153,40)
    0
    0
        N/W to G1 (Parameter: hypophosphatemia) (n=153,41)
    0
    0
        N/W to G2 (Parameter: hypophosphatemia) (n=153,41)
    18
    4
        N/W to G3 (Parameter: hypophosphatemia) (n=153,41)
    2
    1
        N/W to G4 (Parameter: hypophosphatemia) (n=153,41)
    0
    0
        N/W to G1 (Parameter: LI) (n=157,41)
    13
    4
        N/W to G2 (Parameter: LI) (n=157,41)
    9
    3
        N/W to G3 (Parameter: LI) (n=157,41)
    7
    2
        N/W to G4 (Parameter: LI) (n=157,41)
    2
    1
        N/W to G1 (Parameter: SAI) (n=156,41)
    16
    3
        N/W to G2 (Parameter: SAI) (n=156,41)
    1
    2
        N/W to G3 (Parameter: SAI) (n=156,41)
    2
    2
        N/W to G4 (Parameter: SAI) (n=156,41)
    1
    1
    Notes
    [4] - Subjects with available data (n=X, X in category titles) were analyzed.
    [5] - Subjects with available data (n=X, X in category titles) were analyzed.
    No statistical analyses for this end point

    Secondary: Serum Maximum Concentration (Cmax) for Avelumab

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    End point title
    Serum Maximum Concentration (Cmax) for Avelumab
    End point description
    Cmax was defined as maximum observed plasma concentration. The determination method of Cmax was observing directly from data. The avelumab PK concentration analysis set included all subjects (Cohort 1 and Cohort 2 combined) who received at least 1 dose of study intervention and had at least one concentration measurement for avelumab. Number of subjects analyzed = number of subjects evaluable for this OM. Number analyzed = subjects evaluable at the specific time point.
    End point type
    Secondary
    End point timeframe
    One hour post-dose on Day 1 of Cycles 1, 3, 6, 12, 18, 24 and Day 15 of Cycle 1
    End point values
    Avelumab 800 mg Intravenous (IV) Q2W plus talazoparib
    Number of subjects analysed
    199 [6]
    Units: mcg/mL
    geometric mean (geometric coefficient of variation)
        CYCLE1DAY1 (n=161)
    223.0 ± 39
        CYCLE1DAY15 (n=146)
    221.6 ± 38
        CYCLE3DAY1 (n=114)
    225.6 ± 34
        CYCLE6DAY1 (n=79)
    222.3 ± 37
        CYCLE12DAY1 (n=35)
    248.2 ± 25
        CYCLE18DAY1 (n=17)
    265.9 ± 20
        CYCLE24DAY1 (n=9)
    286.1 ± 21
    Notes
    [6] - Subjects with available data (n=X in category titles) were analyzed.
    No statistical analyses for this end point

    Secondary: Serum Lowest (Trough) Concentration (Ctrough) of Avelumab

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    End point title
    Serum Lowest (Trough) Concentration (Ctrough) of Avelumab
    End point description
    Ctrough was defined as predose concentration during multiple dosing. The determination method of Ctrough was observing directly from data. The lower limit of quantification (LLQ) was 0.2 mcg/mL. For Cycle 1 Day 1, as the number of observations above lower limit of quantification (NALQ) = 0, summary statistics were not presented. The avelumab PK concentration analysis set included all subjects (Cohort 1 and Cohort 2 combined) who received at least 1 dose of study intervention and had at least one concentration measurement for avelumab. Number of subjects analyzed = number of subjects evaluable for this OM. Number analyzed = subjects evaluable at the specific time point.
    End point type
    Secondary
    End point timeframe
    Predose on Day 1 of Cycles 1, 3, 6, 12, 18, 24 and Day 15 of Cycle 1
    End point values
    Avelumab 800 mg Intravenous (IV) Q2W plus talazoparib
    Number of subjects analysed
    199 [7]
    Units: microgram(mcg)/milliliter(mL)
    geometric mean (geometric coefficient of variation)
        CYCLE1DAY1 (n=180)
    99999 ± 99999
        CYCLE1DAY15 (n=164)
    21.06 ± 58
        CYCLE3DAY1 (n=110)
    32.65 ± 63
        CYCLE6DAY1 (n=83)
    36.23 ± 60
        CYCLE12DAY1 (n=35)
    41.80 ± 60
        CYCLE18DAY1 (n=16)
    35.19 ± 54
        CYCLE24DAY1 (n=10)
    37.21 ± 54
    Notes
    [7] - 99999 is entered for data not presented. n=subjects analyzed with available data.
    No statistical analyses for this end point

    Secondary: Plasma Ctrough for Talazoparib

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    End point title
    Plasma Ctrough for Talazoparib
    End point description
    Ctrough was defined as predose concentration during multiple dosing. The determination method of Ctrough was observing directly from data. For Cycle 1 Day 1, as the number of observations above lower limit of quantification (NALQ) = 0, summary statistics were not presented. Evaluable subjects were subjects with non-missing Ctrough concentrations at each specific time point and meeting 2 conditions: subjects received 14 consecutive days of talazoparib dose without dosing interruption prior to sample collection (except on Cycle 1 Day 1) and sample collection within 24 hours ± 10% (2 hours and 24 minutes) after the previous day's dose and no more than 5 minutes (0.083 hours) after the administration of the dose on the day of PK sample collection. Predose PK samples on Cycle 1 Day 1 must have been collected prior to dose. The analysis set included all subjects who received at least 1 dose of study intervention and had at least one Ctrough concentration measurement for talazoparib.
    End point type
    Secondary
    End point timeframe
    Predose on Cycle 1 Days 1, 15 and Cycle 3 Day 1
    End point values
    Avelumab 800 mg Intravenous (IV) Q2W plus talazoparib
    Number of subjects analysed
    199 [8]
    Units: picogram(pg)/mL
    geometric mean (geometric coefficient of variation)
        CYCLE1DAY1 (Starting Dose: 1 mg QD) (n=170)
    99999 ± 99999
        CYCLE1DAY15 (Starting Dose: 1 mg QD) (n=62)
    4649 ± 61
        CYCLE3DAY1 (Starting Dose: 1 mg QD) (n=30)
    3313 ± 113
        CYCLE1DAY1 (Starting Dose: 0.75 mg QD) (n=16)
    99999 ± 99999
        CYCLE1DAY15 (Starting Dose: 0.75 mg QD) (n=2)
    7612 ± 99999
        CYCLE3DAY1 (Starting Dose: 0.75 mg QD) (n=4)
    4314 ± 42
    Notes
    [8] - 99999 is entered for data not presented or not estimable. n=subjects analyzed with available data.
    No statistical analyses for this end point

    Secondary: Number of Subjects by Avelumab Anti-drug Antibody (ADA) Categories

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    End point title
    Number of Subjects by Avelumab Anti-drug Antibody (ADA) Categories
    End point description
    Blood samples were assayed for ADA. ADA never-positive=no positive ADA results at any time point. ADA ever-positive=at least one positive ADA result at any time point. Baseline ADA positive=a positive ADA result at baseline. Treatment-boosted ADA=a positive ADA result at baseline and the titer >=8×baseline titer at least once after treatment with avelumab. Treatment-induced ADA=subject was ADA-negative at baseline and had at least one positive post-baseline ADA result; or had at least one positive post-baseline ADA result if no baseline sample. Transient ADA response=subjects with treatment-induced ADA had (a single positive ADA result or duration between first and last positive result <16weeks) and ADA result at the last assessment was not positive. Persistent ADA response=subjects with treatment-induced ADA had duration between first & last positive ADA result >=16weeks or a positive ADA result at the last assessment. Analysis population=subjects with >=1 ADA sample for avelumab.
    End point type
    Secondary
    End point timeframe
    Predose (within 2 hours before start of avelumab infusion) on Day 1 of Cycles 1, 3, 6, 12, 18, 24 and Day 15 of Cycle 1
    End point values
    Cohort 1 (BReast CAncer Gene [BRCA] 1/2 defect) Cohort 2 (Ataxia Telangiectasia Mutated [ATM] defect)
    Number of subjects analysed
    159 [9]
    40 [10]
    Units: Subjects
        ADA never-positive (n=159,40)
    153
    39
        ADA ever-positive (n=159,40)
    6
    1
        Baseline ADA positive (n=150,38)
    5
    1
        Treatment-boosted ADA (n=143,37)
    0
    0
        Treatment-induced ADA (n=147,38)
    1
    0
        Transient ADA response (n=147,38)
    1
    0
        Persistent ADA response (n=147,38)
    0
    0
    Notes
    [9] - Subjects with available data (n=X, X in category titles) were analyzed.
    [10] - Subjects with available data (n=X, X in category titles) were analyzed.
    No statistical analyses for this end point

    Secondary: Plasma Post-dose Concentrations for Talazoparib

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    End point title
    Plasma Post-dose Concentrations for Talazoparib
    End point description
    In this OM, the post-dose concentrations for talazoparib in plasma were reported. The Analysis Population included all subjects (Cohort 1 and Cohort 2 combined) who received at least 1 dose of talazoparib, had at least one non-missing concentration measurement at any collection scheduled time point, received 14 consecutive days of talazoparib dose without dosing interruption prior to sample collection (except on Cycle 1 Day 1) and sample collection was performed within ± 10% (12 minutes) of nominal time post-dose.
    End point type
    Secondary
    End point timeframe
    Postdose (samples collected within 2 hours post dose plus/minus 12 minutes) on Days 1,15 of Cycle 1, and Day 1 of Cycle 3
    End point values
    Avelumab 800 mg Intravenous (IV) Q2W plus talazoparib
    Number of subjects analysed
    106 [11]
    Units: pg/mL
    geometric mean (geometric coefficient of variation)
        CYCLE1DAY1 (Starting Dose: 1 mg QD) (n=76)
    1833 ± 275
        CYCLE1DAY15 (Starting Dose: 1 mg QD) (n=51)
    7985 ± 79
        CYCLE3DAY1 (Starting Dose: 1 mg QD) (n=22)
    7800 ± 69
        CYCLE1DAY1 (Starting Dose: 0.75 mg QD) (n=6)
    1663 ± 100
        CYCLE1DAY15 (Starting Dose: 0.75 mg QD) (n=6)
    12590 ± 47
        CYCLE3DAY1 (Starting Dose: 0.75 mg QD) (n=3)
    8366 ± 53
    Notes
    [11] - Subjects with available data (n=X in category titles) were analyzed.
    No statistical analyses for this end point

    Secondary: Number of Subjects With Neutralizing Antibodies (Nab) Levels Against Avelumab Ever-Positive

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    End point title
    Number of Subjects With Neutralizing Antibodies (Nab) Levels Against Avelumab Ever-Positive
    End point description
    Nab ever-positive was defined as at least one positive Nab result at any time point. Samples positive for ADA with persistent treatment-induced ADA response could be analyzed for Nab. The immunogenicity analysis set included subjects who had at least 1 Nab sample collected for avelumab. Nabs data were not collected due to insufficient number of subjects with persistent treatment-induced ADA response. Therefore, the number of subjects analyzed for this OM was 0.
    End point type
    Secondary
    End point timeframe
    Predose (within 2 hours before start of avelumab infusion) on Day 1 of Cycles 1, 3, 6, 12, 18, 24 and Day 15 of Cycle 1
    End point values
    Cohort 1 (BReast CAncer Gene [BRCA] 1/2 defect) Cohort 2 (Ataxia Telangiectasia Mutated [ATM] defect)
    Number of subjects analysed
    0 [12]
    0 [13]
    Units: Subjects
    Notes
    [12] - Data were not collected due to insufficient subjects with persistent treatment-induced ADA response.
    [13] - Data were not collected due to insufficient subjects with persistent treatment-induced ADA response.
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Confirmed OR as Assessed by The Investigator

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    End point title
    Percentage of Subjects With Confirmed OR as Assessed by The Investigator
    End point description
    For subjects with solid tumors, except mCRPC, OR was defined as a CR or PR per RECIST v1.1, both confirmed by repeat assessments performed no less than 4 weeks after the criteria for response were first met. For subjects with mCRPC, OR was defined as the percentage of subjects with a best overall soft tissue response of CR or PR per RECIST v1.1 with no evidence of confirmed bone disease progression per PCWG3 criteria. Per RECIST v1.1, CR was defined as complete disappearance of all target and non-target lesions with the exception of nodal disease. PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. Non-target PR lesions must be non-PD, where PD was unequivocal progression of pre-existing lesions.
    End point type
    Secondary
    End point timeframe
    From the first dose of study treatment until the date of first documented disease progression or date of death from any cause, whichever comes first, assessed up to approximately 24 months
    End point values
    Cohort 1 (BReast CAncer Gene [BRCA] 1/2 defect) Cohort 2 (Ataxia Telangiectasia Mutated [ATM] defect)
    Number of subjects analysed
    159
    41
    Units: Percentage of subjects
        number (confidence interval 95%)
    34.6 (27.2 to 42.5)
    14.6 (5.6 to 29.2)
    No statistical analyses for this end point

    Secondary: DoR as Assessed by Investigator

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    End point title
    DoR as Assessed by Investigator
    End point description
    For subjects with solid tumors, except mCRPC: DoR was defined for subjects with confirmed objective response (CR or PR) as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. For subjects with mCRPC:DoR was defined for subjects with confirmed objective response (CR or PR) as the time from the first objective evidence of soft tissue response (subsequently confirmed) per RECIST v1.1 and no evidence of confirmed bone disease progression by PCWG3 to the first subsequent objective evidence of radiographic progression or death due to any cause, whichever occurred first. Radiographic progression was defined as soft tissue progression evaluated per RECIST v1.1 or bone disease progression evaluated per PCWG3. The analysis population included all enrolled subjects who received at least 1 dose of study treatment and with confirmed CR or PR as assessed by investigator.
    End point type
    Secondary
    End point timeframe
    Baseline up to approximately 24 months
    End point values
    Cohort 1 (BReast CAncer Gene [BRCA] 1/2 defect) Cohort 2 (Ataxia Telangiectasia Mutated [ATM] defect)
    Number of subjects analysed
    55
    6
    Units: Months
        median (confidence interval 95%)
    8.8 (7.5 to 10.7)
    7.1 (5.5 to 9.7)
    No statistical analyses for this end point

    Secondary: Duration of Response (DoR) as Assessed by BICR

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    End point title
    Duration of Response (DoR) as Assessed by BICR
    End point description
    For subjects with solid tumors, except mCRPC: DoR was defined for subjects with confirmed objective response (CR or PR) as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause, whichever occured first. For subjects with mCRPC: DoR was defined for subjects with confirmed objective response (CR or PR) as the time from the first objective evidence of soft tissue response (subsequently confirmed) per RECIST v1.1 and no evidence of confirmed bone disease progression by PCWG3 to the first subsequent objective evidence of radiographic progression or death due to any cause, whichever occured first. Radiographic progression was defined as soft tissue progression evaluated per RECIST v1.1 or bone disease progression evaluated per PCWG3. The analysis population included all enrolled subjects who received at least 1 dose of study treatment and with confirmed CR or PR as assessed by BICR.
    End point type
    Secondary
    End point timeframe
    Baseline up to approximately 24 months
    End point values
    Cohort 1 (BReast CAncer Gene [BRCA] 1/2 defect) Cohort 2 (Ataxia Telangiectasia Mutated [ATM] defect)
    Number of subjects analysed
    44 [14]
    3 [15]
    Units: Months
        median (confidence interval 95%)
    12.5 (7.5 to 99999)
    99999 (6.7 to 99999)
    Notes
    [14] - Reason for 99999: the upper limit of the confidence interval (CI) is not crossing the 50% bound.
    [15] - Reason for 99999: the median and upper limit of the CI are not crossing the 50% bound.
    No statistical analyses for this end point

    Secondary: TTR as Assessed by Investigator

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    End point title
    TTR as Assessed by Investigator
    End point description
    For subjects with solid tumors, except mCRPC: TTR was defined for subjects with confirmed objective response (CR or PR) as the time from the first dose of study treatment to the first documentation of objective tumor response. For subjects with mCRPC: TTR was defined as the time from the first dose of study treatment to the first objective evidence of soft tissue response with no evidence of confirmed bone disease progression on bone scan per PCWG3. Soft tissue response was defined as a BOR of CR or PR per RECIST v1.1. The analysis population included all enrolled subjects who received at least 1 dose of study treatment and with confirmed CR or PR as assessed by investigator.
    End point type
    Secondary
    End point timeframe
    Baseline up to approximately 24 months
    End point values
    Cohort 1 (BReast CAncer Gene [BRCA] 1/2 defect) Cohort 2 (Ataxia Telangiectasia Mutated [ATM] defect)
    Number of subjects analysed
    55
    6
    Units: Months
        median (full range (min-max))
    1.84 (1.5 to 18.4)
    3.99 (1.9 to 14.0)
    No statistical analyses for this end point

    Secondary: Time to Tumor Response (TTR) as Assessed by BICR

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    End point title
    Time to Tumor Response (TTR) as Assessed by BICR
    End point description
    For subjects with solid tumors, except mCRPC: TTR was defined for subjects with confirmed objective response (CR or PR) as the time from the first dose of study treatment to the first documentation of objective tumor response. For subjects with mCRPC: TTR was defined as the time from the first dose of study treatment to the first objective evidence of soft tissue response with no evidence of confirmed bone disease progression on bone scan per PCWG3. Soft tissue response was defined as a Best Overall Response (BOR) of CR or PR per RECIST v1.1. The analysis population included all enrolled subjects who received at least 1 dose of study treatment and with confirmed CR or PR as assessed by BICR.
    End point type
    Secondary
    End point timeframe
    Baseline up to approximately 24 months
    End point values
    Cohort 1 (BReast CAncer Gene [BRCA] 1/2 defect) Cohort 2 (Ataxia Telangiectasia Mutated [ATM] defect)
    Number of subjects analysed
    44
    3
    Units: Months
        median (full range (min-max))
    1.82 (1.5 to 12.1)
    5.52 (1.6 to 16.8)
    No statistical analyses for this end point

    Secondary: Overall Survival (OS) for All Subjects

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    End point title
    Overall Survival (OS) for All Subjects
    End point description
    OS was defined as the time from the first dose of study treatment to the date of death. Subjects without an event (death) were censored at the date of last contact. All efficacy analyses were performed based on the full analysis set. The full analysis set included all enrolled subjects who received at least 1 dose of study treatment. Subjects were classified according to the cohort assigned at enrollment.
    End point type
    Secondary
    End point timeframe
    Baseline up to approximately 24 months
    End point values
    Cohort 1 (BReast CAncer Gene [BRCA] 1/2 defect) Cohort 2 (Ataxia Telangiectasia Mutated [ATM] defect)
    Number of subjects analysed
    159
    41
    Units: Months
        median (confidence interval 95%)
    11.9 (10.1 to 13.7)
    16.4 (12.8 to 21.9)
    No statistical analyses for this end point

    Secondary: PFS as Assessed by Investigator

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    End point title
    PFS as Assessed by Investigator
    End point description
    For subjects with solid tumors, except mCRPC: PFS was defined as the time from the first dose of study treatment to the date of disease progression by RECIST v1.1 or death due to any cause, whichever occurred first. For subjects with mCRPC: PFS was defined as the time from the first dose of study treatment to documentation of radiographic progression in soft tissue evaluated per RECIST v1.1, in bone evaluated per PCWG3, or death, whichever occurred first. All efficacy analyses were performed based on the full analysis set. The full analysis set included all enrolled subjects who received at least 1 dose of study treatment. Subjects were classified according to the cohort assigned at enrollment.
    End point type
    Secondary
    End point timeframe
    Baseline up to approximately 24 months
    End point values
    Cohort 1 (BReast CAncer Gene [BRCA] 1/2 defect) Cohort 2 (Ataxia Telangiectasia Mutated [ATM] defect)
    Number of subjects analysed
    159
    41
    Units: Months
        median (confidence interval 95%)
    5.3 (3.7 to 5.6)
    3.7 (2.1 to 7.4)
    No statistical analyses for this end point

    Secondary: Progression Free Survival (PFS) as Assessed by BICR

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    End point title
    Progression Free Survival (PFS) as Assessed by BICR
    End point description
    For subjects with solid tumors, except mCRPC: PFS was defined as the time from the first dose of study treatment to the date of disease progression by RECIST v1.1 or death due to any cause, whichever occurred first. For subjects with mCRPC: PFS was defined as the time from the first dose of study treatment to documentation of radiographic progression in soft tissue evaluated per RECIST v1.1, in bone evaluated per PCWG3, or death, whichever occurred first. All efficacy analyses were performed based on the full analysis set. The full analysis set included all enrolled subjects who received at least 1 dose of study treatment. Subjects were classified according to the cohort assigned at enrollment.
    End point type
    Secondary
    End point timeframe
    Baseline up to approximately 24 months
    End point values
    Cohort 1 (BReast CAncer Gene [BRCA] 1/2 defect) Cohort 2 (Ataxia Telangiectasia Mutated [ATM] defect)
    Number of subjects analysed
    159
    41
    Units: Months
        median (confidence interval 95%)
    3.7 (3.1 to 5.4)
    3.5 (1.8 to 5.5)
    No statistical analyses for this end point

    Secondary: Number of Subjects With Confirmed PSA Response

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    End point title
    Number of Subjects With Confirmed PSA Response
    End point description
    For subjects with mCRPC, PSA response was defined as confirmed PSA decline >=50% compared to baseline. PSA response was calculated as a decline from baseline PSA (ng/mL) to the maximal PSA response with a threshold of 50%. A PSA response must have been confirmed by a second consecutive value at least 3 weeks later. The analysis population included all subjects with mCRPC who received at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    Baseline up to approximately 24 months
    End point values
    Cohort 1 (BReast CAncer Gene [BRCA] 1/2 defect) Cohort 2 (Ataxia Telangiectasia Mutated [ATM] defect)
    Number of subjects analysed
    26
    5
    Units: Subjects
    17
    2
    No statistical analyses for this end point

    Secondary: Time to Prostate-Specific Antigen (PSA) Progression for Subjects With mCRPC

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    End point title
    Time to Prostate-Specific Antigen (PSA) Progression for Subjects With mCRPC
    End point description
    For subjects with mCRPC, time to PSA progression was defined as the time from the first dose to the date that a >=25% increase in PSA with an absolute increase of >=2 μg/L (2 ng/mL) above the nadir (or baseline for subjects with no PSA decline) was documented, confirmed by a second consecutive PSA value obtained >=3 weeks (21 days) later. The analysis population included all subjects with mCRPC who received at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    Baseline up to approximately 24 months
    End point values
    Cohort 1 (BReast CAncer Gene [BRCA] 1/2 defect) Cohort 2 (Ataxia Telangiectasia Mutated [ATM] defect)
    Number of subjects analysed
    26
    5 [16]
    Units: Months
        median (confidence interval 95%)
    6.5 (3.7 to 12.7)
    11.3 (3.7 to 99999)
    Notes
    [16] - The upper limit of the CI is not crossing the 50% bound, thus 99999 is entered.
    No statistical analyses for this end point

    Secondary: Number of Subjects With Circulating Tumor Cell (CTC) Count Conversion

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    End point title
    Number of Subjects With Circulating Tumor Cell (CTC) Count Conversion
    End point description
    For subjects with mCRPC, CTC count conversion was defined as a decrease in CTC count from >=5 CTC per 7.5 mL of blood at baseline to <5 CTC per 7.5 mL of blood anytime on study. The analysis population included all enrolled subjects with mCRPC who received at least 1 dose of study treatment, and with CTC count >=5 CTC per 7.5 mL of blood at baseline.
    End point type
    Secondary
    End point timeframe
    Day 1 of Cycle 1 to Cycle 4
    End point values
    Cohort 1 (BReast CAncer Gene [BRCA] 1/2 defect) Cohort 2 (Ataxia Telangiectasia Mutated [ATM] defect)
    Number of subjects analysed
    13
    2
    Units: Subjects
    11
    1
    No statistical analyses for this end point

    Secondary: Number of Subjects With Cancer Antigen 125 (CA-125) Response

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    End point title
    Number of Subjects With Cancer Antigen 125 (CA-125) Response
    End point description
    For subjects with ovarian cancer, CA-125 response was defined as at least a 50% reduction in CA-125 levels from baseline. The response must have been confirmed and maintained for at least 28 days. The analysis population included all subjects with ovarian cancer who received at least 1 dose of study intervention.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 1 of each treatment Cycle, maximum up to 4.3 years approximately
    End point values
    Cohort 1 (BReast CAncer Gene [BRCA] 1/2 defect) Cohort 2 (Ataxia Telangiectasia Mutated [ATM] defect)
    Number of subjects analysed
    26
    3
    Units: Subjects
    9
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects With Positive Programmed Death Ligand 1 (PD-L1) Expression in Baseline Tumor Tissue

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    End point title
    Number of Subjects With Positive Programmed Death Ligand 1 (PD-L1) Expression in Baseline Tumor Tissue
    End point description
    PD-L1 expression on tumor and infiltrating immune cells was measured by immunohistochemistry (IHC). PD-L1 expression level was defined as the number of PD-L1 positive cells and/or qualitative assessment of PD-L1 staining on tumor and inflammatory cells in regions of interest. This OM reported the number of subjects classified as positive according to scoring algorithms and cut-offs established from external sources. The biomarker analysis set included all subjects who received at least 1 dose of study treatment and had at least 1 screening biomarker assessment.
    End point type
    Secondary
    End point timeframe
    Baseline
    End point values
    Cohort 1 (BReast CAncer Gene [BRCA] 1/2 defect) Cohort 2 (Ataxia Telangiectasia Mutated [ATM] defect)
    Number of subjects analysed
    159
    41
    Units: Subjects
    27
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects With Different Status for Defects in BRCA1, BRCA2 and ATM

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    End point title
    Number of Subjects With Different Status for Defects in BRCA1, BRCA2 and ATM
    End point description
    Subjects were enrolled in the two cohorts based on BRCA 1/2 and ATM defect status assessed by the local laboratory. The subject BRCA and ATM status was assessed retrospectively by central laboratory, that may differ from the status assessed by the local laboratory. The ATM subjects with a negative ATM status per the central laboratory were reported to have a positive ATM status per the local laboratory. Therefore, subjects with negative ATM status might have been included in the ATM defect cohort. For defects in BRCA1, BRCA2 and ATM by central laboratory analysis, subjects were classified as positive, negative, not analyzable or missing. The number of subjects in each category of BRCA 1 defect, BRCA 2 defect, BRCA 1 or BRCA 2 defect and ATM defect were presented. The biomarker analysis set included all subjects who received at least 1 dose of study treatment and had at least 1 screening biomarker assessment.
    End point type
    Secondary
    End point timeframe
    Baseline
    End point values
    Cohort 1 (BReast CAncer Gene [BRCA] 1/2 defect) Cohort 2 (Ataxia Telangiectasia Mutated [ATM] defect)
    Number of subjects analysed
    159
    41
    Units: Subjects
        BRCA1 status positive
    52
    0
        BRCA1 status negative
    65
    29
        BRCA1 status not analyzable
    21
    4
        BRCA1 status missing
    21
    8
        BRCA2 status positive
    53
    1
        BRCA2 status negative
    64
    28
        BRCA2 status not analyzable
    21
    4
        BRCA2 status missing
    21
    8
        BRCA status positive
    105
    1
        BRCA status negative
    12
    28
        BRCA status not analyzable
    21
    4
        BRCA status missing
    21
    8
        ATM status positive
    2
    26
        ATM status negative
    115
    3
        ATM status not analyzable
    21
    4
        ATM status missing
    21
    8
    No statistical analyses for this end point

    Secondary: Number of Subjects by Status of Tumor Mutational Burden (TMB) at Baseline

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    End point title
    Number of Subjects by Status of Tumor Mutational Burden (TMB) at Baseline
    End point description
    TMB was defined as the total number of mutations in the tumor genome, or number of mutations per megabase of DNA if derived from targeted sequencing. TMB categories were defined as high, low for a number of mutations per megabase >=10 and <10, respectively. The TMB category ‘Not analyzable’ included subjects with available samples but not evaluable. The TMB category ‘Missing’ included subjects with no sample available. The number of subjects in each category at only baseline were tabulated. The biomarker analysis set included all subjects who received at least 1 dose of study treatment and had at least 1 screening biomarker assessment.
    End point type
    Secondary
    End point timeframe
    Baseline
    End point values
    Cohort 1 (BReast CAncer Gene [BRCA] 1/2 defect) Cohort 2 (Ataxia Telangiectasia Mutated [ATM] defect)
    Number of subjects analysed
    159
    41
    Units: Subjects
        TMB status high
    9
    2
        TMB status low
    95
    23
        TMB status not analyzable
    34
    8
        TMB status missing
    21
    8
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From baseline up to 30 days after last dose of study treatment, maximum up to 4.3 years approximately.
    Adverse event reporting additional description
    The same event may appear as both an AE and an SAE. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Total number at risk below refers to the number of subjects evaluable for SAEs or AEs.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    25.1
    Reporting groups
    Reporting group title
    Cohort 2 (ATM defect)
    Reporting group description
    Subjects with locally advanced or metastatic solid tumors with one or more defects in the ATM gene without concurrent BRCA1/2 defect were enrolled in Cohort 2. Talazoparib was self-administered orally at a starting dose of 1 mg QD for subjects with normal renal function or mild renal impairment until End of Treatment. Subjects with moderate renal impairment received starting dose of 0.75 mg QD. Avelumab was administered as a 1-hour IV infusion Q2W on Days 1 and 15 of each 28-day cycle at a dose of 800 mg after administration of talazoparib and the premedication.

    Reporting group title
    Cohort 1 (BRCA 1/2 defect)
    Reporting group description
    Subjects with locally advanced or metastatic solid tumors with one or more defects in the BRCA1 or BRCA2 genes were enrolled in Cohort 1. Talazoparib was self-administered orally at a starting dose of 1 mg QD for subjects with normal renal function or mild renal impairment until End of Treatment. Subjects with moderate renal impairment received starting dose of 0.75 mg QD. Avelumab was administered as a 1-hour IV infusion Q2W on Days 1 and 15 of each 28-day cycle at a dose of 800 mg after administration of talazoparib and the premedication.

    Serious adverse events
    Cohort 2 (ATM defect) Cohort 1 (BRCA 1/2 defect)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    7 / 41 (17.07%)
    50 / 159 (31.45%)
         number of deaths (all causes)
    3
    15
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasm progression
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to meninges
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Malignant neoplasm progression
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cancer pain
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Hypotension
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Disease progression
         subjects affected / exposed
    2 / 41 (4.88%)
    8 / 159 (5.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 41 (2.44%)
    2 / 159 (1.26%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Pelvic pain
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         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
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pulmonary embolism
         subjects affected / exposed
    0 / 41 (0.00%)
    3 / 159 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 41 (0.00%)
    3 / 159 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    2 / 41 (4.88%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    3 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    2 / 41 (4.88%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    5 / 6
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Weight decreased
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Troponin T increased
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutrophil count decreased
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver function test increased
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Fracture
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infusion related reaction
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Atrioventricular block complete
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block second degree
         subjects affected / exposed
    0 / 41 (0.00%)
    2 / 159 (1.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Syncope
         subjects affected / exposed
    0 / 41 (0.00%)
    2 / 159 (1.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Migraine
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depressed level of consciousness
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         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 / 41 (4.88%)
    4 / 159 (2.52%)
         occurrences causally related to treatment / all
    2 / 2
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone marrow disorder
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    1 / 41 (2.44%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    4 / 4
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    0 / 41 (0.00%)
    2 / 159 (1.26%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Eye disorder
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    0 / 41 (0.00%)
    3 / 159 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Nausea
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Obstruction gastric
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal perforation
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestine polyp
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subileus
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 41 (0.00%)
    2 / 159 (1.26%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug-induced liver injury
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune-mediated hepatitis
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Jaundice
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver injury
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Urinary tract obstruction
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urethral obstruction
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureterolithiasis
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureteric obstruction
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute kidney injury
         subjects affected / exposed
    1 / 41 (2.44%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Musculoskeletal and connective tissue disorders
    Osteitis
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myositis
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal wall abscess
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacterial abdominal infection
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Clostridial infection
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 41 (2.44%)
    4 / 159 (2.52%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 41 (0.00%)
    3 / 159 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 41 (2.44%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    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
    Cohort 2 (ATM defect) Cohort 1 (BRCA 1/2 defect)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    40 / 41 (97.56%)
    153 / 159 (96.23%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain
         subjects affected / exposed
    3 / 41 (7.32%)
    2 / 159 (1.26%)
         occurrences all number
    4
    4
    Vascular disorders
    Hot flush
         subjects affected / exposed
    3 / 41 (7.32%)
    1 / 159 (0.63%)
         occurrences all number
    3
    1
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    2 / 41 (4.88%)
    27 / 159 (16.98%)
         occurrences all number
    2
    57
    Chills
         subjects affected / exposed
    5 / 41 (12.20%)
    17 / 159 (10.69%)
         occurrences all number
    6
    22
    Fatigue
         subjects affected / exposed
    19 / 41 (46.34%)
    50 / 159 (31.45%)
         occurrences all number
    23
    89
    Influenza like illness
         subjects affected / exposed
    2 / 41 (4.88%)
    10 / 159 (6.29%)
         occurrences all number
    2
    12
    Oedema peripheral
         subjects affected / exposed
    4 / 41 (9.76%)
    12 / 159 (7.55%)
         occurrences all number
    4
    13
    Pyrexia
         subjects affected / exposed
    3 / 41 (7.32%)
    28 / 159 (17.61%)
         occurrences all number
    4
    35
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    5 / 41 (12.20%)
    19 / 159 (11.95%)
         occurrences all number
    6
    23
    Dyspnoea
         subjects affected / exposed
    8 / 41 (19.51%)
    34 / 159 (21.38%)
         occurrences all number
    9
    53
    Nasal congestion
         subjects affected / exposed
    1 / 41 (2.44%)
    10 / 159 (6.29%)
         occurrences all number
    1
    11
    Productive cough
         subjects affected / exposed
    3 / 41 (7.32%)
    8 / 159 (5.03%)
         occurrences all number
    3
    10
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    5 / 41 (12.20%)
    21 / 159 (13.21%)
         occurrences all number
    6
    22
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    7 / 41 (17.07%)
    16 / 159 (10.06%)
         occurrences all number
    11
    27
    Aspartate aminotransferase increased
         subjects affected / exposed
    6 / 41 (14.63%)
    18 / 159 (11.32%)
         occurrences all number
    13
    31
    Blood bilirubin increased
         subjects affected / exposed
    3 / 41 (7.32%)
    8 / 159 (5.03%)
         occurrences all number
    5
    12
    Blood creatine phosphokinase increased
         subjects affected / exposed
    4 / 41 (9.76%)
    7 / 159 (4.40%)
         occurrences all number
    12
    8
    Blood creatinine increased
         subjects affected / exposed
    5 / 41 (12.20%)
    3 / 159 (1.89%)
         occurrences all number
    10
    5
    Lymphocyte count decreased
         subjects affected / exposed
    3 / 41 (7.32%)
    2 / 159 (1.26%)
         occurrences all number
    4
    21
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    3 / 41 (7.32%)
    9 / 159 (5.66%)
         occurrences all number
    3
    21
    Neutrophil count decreased
         subjects affected / exposed
    5 / 41 (12.20%)
    21 / 159 (13.21%)
         occurrences all number
    10
    55
    Weight decreased
         subjects affected / exposed
    2 / 41 (4.88%)
    10 / 159 (6.29%)
         occurrences all number
    3
    13
    White blood cell count decreased
         subjects affected / exposed
    4 / 41 (9.76%)
    12 / 159 (7.55%)
         occurrences all number
    9
    24
    Platelet count decreased
         subjects affected / exposed
    11 / 41 (26.83%)
    25 / 159 (15.72%)
         occurrences all number
    19
    71
    Injury, poisoning and procedural complications
    Infusion related reaction
         subjects affected / exposed
    3 / 41 (7.32%)
    22 / 159 (13.84%)
         occurrences all number
    3
    23
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    1 / 41 (2.44%)
    19 / 159 (11.95%)
         occurrences all number
    1
    24
    Headache
         subjects affected / exposed
    6 / 41 (14.63%)
    35 / 159 (22.01%)
         occurrences all number
    6
    48
    Peripheral sensory neuropathy
         subjects affected / exposed
    3 / 41 (7.32%)
    5 / 159 (3.14%)
         occurrences all number
    3
    5
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    4 / 41 (9.76%)
    20 / 159 (12.58%)
         occurrences all number
    6
    57
    Anaemia
         subjects affected / exposed
    18 / 41 (43.90%)
    81 / 159 (50.94%)
         occurrences all number
    52
    269
    Thrombocytopenia
         subjects affected / exposed
    5 / 41 (12.20%)
    27 / 159 (16.98%)
         occurrences all number
    8
    62
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    6 / 41 (14.63%)
    5 / 159 (3.14%)
         occurrences all number
    6
    5
    Abdominal pain
         subjects affected / exposed
    6 / 41 (14.63%)
    30 / 159 (18.87%)
         occurrences all number
    8
    42
    Ascites
         subjects affected / exposed
    3 / 41 (7.32%)
    1 / 159 (0.63%)
         occurrences all number
    3
    2
    Constipation
         subjects affected / exposed
    8 / 41 (19.51%)
    39 / 159 (24.53%)
         occurrences all number
    10
    52
    Diarrhoea
         subjects affected / exposed
    10 / 41 (24.39%)
    36 / 159 (22.64%)
         occurrences all number
    16
    75
    Dyspepsia
         subjects affected / exposed
    3 / 41 (7.32%)
    10 / 159 (6.29%)
         occurrences all number
    3
    11
    Nausea
         subjects affected / exposed
    21 / 41 (51.22%)
    73 / 159 (45.91%)
         occurrences all number
    27
    102
    Vomiting
         subjects affected / exposed
    11 / 41 (26.83%)
    39 / 159 (24.53%)
         occurrences all number
    16
    48
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    3 / 41 (7.32%)
    19 / 159 (11.95%)
         occurrences all number
    3
    20
    Pruritus
         subjects affected / exposed
    1 / 41 (2.44%)
    10 / 159 (6.29%)
         occurrences all number
    1
    13
    Dry skin
         subjects affected / exposed
    4 / 41 (9.76%)
    5 / 159 (3.14%)
         occurrences all number
    5
    5
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    5 / 41 (12.20%)
    10 / 159 (6.29%)
         occurrences all number
    8
    11
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    11 / 41 (26.83%)
    30 / 159 (18.87%)
         occurrences all number
    13
    37
    Back pain
         subjects affected / exposed
    10 / 41 (24.39%)
    21 / 159 (13.21%)
         occurrences all number
    16
    23
    Myalgia
         subjects affected / exposed
    2 / 41 (4.88%)
    16 / 159 (10.06%)
         occurrences all number
    2
    18
    Neck pain
         subjects affected / exposed
    2 / 41 (4.88%)
    9 / 159 (5.66%)
         occurrences all number
    3
    12
    Pain in extremity
         subjects affected / exposed
    5 / 41 (12.20%)
    7 / 159 (4.40%)
         occurrences all number
    5
    11
    Infections and infestations
    Sinusitis
         subjects affected / exposed
    3 / 41 (7.32%)
    1 / 159 (0.63%)
         occurrences all number
    3
    1
    Upper respiratory tract infection
         subjects affected / exposed
    3 / 41 (7.32%)
    12 / 159 (7.55%)
         occurrences all number
    3
    13
    Urinary tract infection
         subjects affected / exposed
    7 / 41 (17.07%)
    11 / 159 (6.92%)
         occurrences all number
    8
    14
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    12 / 41 (29.27%)
    33 / 159 (20.75%)
         occurrences all number
    19
    41
    Hypokalaemia
         subjects affected / exposed
    5 / 41 (12.20%)
    8 / 159 (5.03%)
         occurrences all number
    11
    13

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    15 Nov 2018
    1. Based on limitations in utility of this and/or complexity to collect this exploratory endpoint, irRECIST assessments and any associated elements were removed or revised accordingly. 2. To help facilitate study conduct, the Schedule of Activities has been modified with a -1 day window for the baseline physical examination and a +/ 3 day window (formerly +/- 2 day) for treatment visits. 3. To help facilitate study conduct, the Schedule of Activities and Section 7.8 has been modified to clarify that Patient Reported Outcome assessments are not required when not available in a language understood by the patient, and to provide a window for shipment of pre-treatment tumor tissue. 4. The background section has been updated with health authority approvals for Avelumab and Talazoparib. 5. Consistent with the updated Avelumab Investigator’s Brochure (version 8, 16 May 2018), the protocol was revised to update background information and recommendation for management of Grade 1 to 2 immune-related rash was updated. 6. Consistent with the updated Talazoparib Investigator’s Brochure (dated August 2018), the protocol was revised to provide updated background information on clinical experience and pharmacokinetic information, to increase the duration of contraception use, and to simplify language regarding prohibited medication P-gp inhibitors. 7. Preliminary safety information and the recommended phase 2 dose from the B9991025 study has been added to the Background, Allocation to Treatment and Talazoparib administration sections. 8. Use of a Patient Enrollment Verification Form has been added.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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