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    Clinical Trial Results:
    A Phase 2 Study of ZEN003694 in Combination with Talazoparib in Patients with Triple-Negative Breast Cancer

    Summary
    EudraCT number
    		 2018-003906-26
    Trial protocol
    		 BE   ES  
    Global end of trial date
    21 Jun 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    29 May 2026
    First version publication date
    29 May 2026
    Other versions
    Summary report(s)
    		 ZEN003694-004 Protocol for EudraCT
    ZEN003694-004_CSR Report_Synopsis_EudraCT_15Mar2024

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    ZEN003694-004
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03901469
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 IND (China -for Expansion phase only): JXHL2000118, IND (China -for Expansion phase only): JXHL2000119, IND (USA): 141108
    Sponsors
    Sponsor organisation name
    Zenith Epigenetics Ltd.
    Sponsor organisation address
    300, 4820 Richard Road SW , Calgary, Alberta T3E 6L1 , Canada,
    Public contact
    Clinical Trial Information, Zenith Epigenetics Ltd., 1 587390-7865, ZEN003694-004@zenithepigenetics.com
    Scientific contact
    Clinical Trial Information, Zenith Epigenetics Ltd., 1 587390-7865, ZEN003694-004@zenithepigenetics.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
    08 Mar 2024
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    08 Mar 2024
    Global end of trial reached?
    Yes
    Global end of trial date
    21 Jun 2024
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    Part 1: To determine the safety, tolerability, maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of ZEN003694 in combination with talazoparib in patients with locally advanced or metastatic triple-negative breast cancer (TNBC) Part 2: To evaluate the efficacy of ZEN003694 in combination with talazoparib in patients with locally advanced or metastatic TNBC Expansion: To evaluate the efficacy of ZEN003694 in combination with talazoparib in patients with locally advanced or metastatic TNBC whose cancer was hormone receptor negative (<5%) at the time of initial breast cancer diagnosis and who have received TROP2-ADC therapy in the unresectable locally advanced or metastatic disease setting.
    Protection of trial subjects
    Managed through Institutional Review Boards, informed patient consent and data confidentiality protocols, as well as routine monitoring of clinical sites.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Apr 2019
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 19
    Country: Number of subjects enrolled
    Belgium: 22
    Country: Number of subjects enrolled
    United States: 42
    Country: Number of subjects enrolled
    China: 32
    Worldwide total number of subjects
    115
    EEA total number of subjects
    41
    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)
    93
    From 65 to 84 years
    22
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 The study was conducted at nineteen investigational sites in the United States (eight), Belgium (two), Spain (two), and China (seven) between June 2019 and March 2024.

    Pre-assignment
    Screening details
    		 Participants ≥ 18 years with metastatic or recurrent or locally advanced TNBC without germline mutations in BRCA1 or BRCA2.

    Period 1
    Period 1 title
    Between June 2019 and March 2024 (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 Part 1 Dose Escalation Cohort 1
    Arm description
    		 ZEN003694 48 mg PO QD with Talazoparib 1 mg PO QD in 28-day cycles. Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in the US and EU.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ZEN003694
    Investigational medicinal product code
    Other name
    ZEN-3694
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    48 mg ZEN003694 PO QD

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Talzenna
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    1 mg Talazoparib PO QD

    Arm title
    		 Part 1 Dose Escalation Cohort 2
    Arm description
    		 ZEN003694 48 mg PO QD with Talazoparib 0.75 mg PO QD in 28-day cycles. Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in the US and EU.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ZEN003694
    Investigational medicinal product code
    Other name
    ZEN-3694
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    48 mg ZEN003694 PO QD

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Talzenna
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    0.75 mg Talazoparib PO QD

    Arm title
    		 Part 1 Dose Escalation Cohort 3
    Arm description
    		 ZEN003694 36 mg PO QD with Talazoparib 1 mg PO QD in 28-day cycles. Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in the US and EU.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ZEN003694
    Investigational medicinal product code
    Other name
    ZEN-3694
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    36 mg ZEN003694 PO QD

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Talzenna
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    1 mg Talazoparib PO QD

    Arm title
    		 Part 2 Stages 1 and 2
    Arm description
    		 ZEN003694 48 mg PO QD with Talazoparib 0.75 mg PO QD in 28-day cycles. Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in the US and EU.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ZEN003694
    Investigational medicinal product code
    Other name
    ZEN-3694
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    48 mg ZEN003694 PO QD

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Talzenna
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    0.75 mg Talazoparib PO QD

    Arm title
    		 Expansion Cohort A
    Arm description
    		 Combination Treatment in Post-TROP2-ADC Patients. ZEN003694 48 mg PO QD with Talazoparib 0.75 mg PO QD (RP2D) in 28-day cycles. Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in the US and EU.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ZEN003694
    Investigational medicinal product code
    Other name
    ZEN-3694
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    48 mg ZEN003694 PO QD

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Talzenna
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    0.75 mg Talazoparib PO QD

    Arm title
    		 Expansion Cohort B - ZEN003694 Monotherapy
    Arm description
    		 ZEN003694 48 mg PO QD as monotherapy at the in 28-day cycles with the option to cross-over to combination treatment of ZEN003694 48 mg PO QD with 0.75 mg Talazoparib PO QD at the time of disease progression (but no sooner than after 6 weeks of monotherapy). Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in the US and EU.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ZEN003694
    Investigational medicinal product code
    Other name
    ZEN-3694
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    48 mg ZEN003694 PO QD

    Arm title
    		 Expansion Cohort C
    Arm description
    		 Combination Treatment in TROP2-ADC-naïve patients. ZEN003694 48 mg PO QD with Talazoparib PO QD (RP2D) in 28-day cycles. Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in China only.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ZEN003694
    Investigational medicinal product code
    Other name
    ZEN-3694
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    48 mg ZEN003694 PO QD

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Talzenna
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    0.75 mg Talazoparib PO QD

    Arm title
    		 Expansion Cohort B - Cross-over Combination
    Arm description
    		 Post cross-over to combination treatment of ZEN003694 48 mg PO QD with 0.75 mg Talazoparib PO QD at the time of disease progression (but no sooner than after 6 weeks of monotherapy). Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in the US and EU.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ZEN003694
    Investigational medicinal product code
    Other name
    ZEN-3694
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    48 mg ZEN003694 PO QD

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Talzenna
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    0.75 mg Talazoparib PO QD

    Number of subjects in period 1
    		Part 1 Dose Escalation Cohort 1 Part 1 Dose Escalation Cohort 2 Part 1 Dose Escalation Cohort 3 Part 2 Stages 1 and 2 Expansion Cohort A Expansion Cohort B - ZEN003694 Monotherapy Expansion Cohort C Expansion Cohort B - Cross-over Combination
    Started
    6
    8
    3
    42
    21
    3
    32
    1
    Completed
    0
    0
    0
    0
    0
    0
    0
    0
    Not completed
    6
    8
    3
    42
    21
    3
    32
    1
         Consent withdrawn by subject
    -
    -
    -
    -
    2
    -
    8
    -
         Adverse event, non-fatal
    1
    -
    -
    -
    -
    -
    9
    -
         Death
    -
    -
    -
    3
    5
    -
    1
    -
         Termination of study by sponsor
    -
    -
    -
    -
    1
    1
    -
    -
         not disclosed
    1
    -
    -
    1
    -
    -
    1
    -
         Withdrawal by Physician
    -
    -
    -
    1
    -
    -
    -
    -
         Clinical Progression
    -
    2
    -
    7
    6
    -
    2
    -
         Radiographic Progression
    4
    6
    3
    30
    7
    2
    11
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Part 1 Dose Escalation Cohort 1
    Reporting group description
    		 ZEN003694 48 mg PO QD with Talazoparib 1 mg PO QD in 28-day cycles. Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in the US and EU.

    Reporting group title
    Part 1 Dose Escalation Cohort 2
    Reporting group description
    		 ZEN003694 48 mg PO QD with Talazoparib 0.75 mg PO QD in 28-day cycles. Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in the US and EU.

    Reporting group title
    Part 1 Dose Escalation Cohort 3
    Reporting group description
    		 ZEN003694 36 mg PO QD with Talazoparib 1 mg PO QD in 28-day cycles. Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in the US and EU.

    Reporting group title
    Part 2 Stages 1 and 2
    Reporting group description
    		 ZEN003694 48 mg PO QD with Talazoparib 0.75 mg PO QD in 28-day cycles. Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in the US and EU.

    Reporting group title
    Expansion Cohort A
    Reporting group description
    		 Combination Treatment in Post-TROP2-ADC Patients. ZEN003694 48 mg PO QD with Talazoparib 0.75 mg PO QD (RP2D) in 28-day cycles. Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in the US and EU.

    Reporting group title
    Expansion Cohort B - ZEN003694 Monotherapy
    Reporting group description
    		 ZEN003694 48 mg PO QD as monotherapy at the in 28-day cycles with the option to cross-over to combination treatment of ZEN003694 48 mg PO QD with 0.75 mg Talazoparib PO QD at the time of disease progression (but no sooner than after 6 weeks of monotherapy). Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in the US and EU.

    Reporting group title
    Expansion Cohort C
    Reporting group description
    		 Combination Treatment in TROP2-ADC-naïve patients. ZEN003694 48 mg PO QD with Talazoparib PO QD (RP2D) in 28-day cycles. Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in China only.

    Reporting group title
    Expansion Cohort B - Cross-over Combination
    Reporting group description
    		 Post cross-over to combination treatment of ZEN003694 48 mg PO QD with 0.75 mg Talazoparib PO QD at the time of disease progression (but no sooner than after 6 weeks of monotherapy). Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in the US and EU.

    Reporting group values
    		 Part 1 Dose Escalation Cohort 1 Part 1 Dose Escalation Cohort 2 Part 1 Dose Escalation Cohort 3 Part 2 Stages 1 and 2 Expansion Cohort A Expansion Cohort B - ZEN003694 Monotherapy Expansion Cohort C Expansion Cohort B - Cross-over Combination Total
    Number of subjects
    		 6 8 3 42 21 3 32 1 115
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 4 7 3 33 19 2 25 1 93
        From 65-84 years
    		 2 1 0 9 2 1 7 0 22
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 57.2 ( 14.8 ) 52.8 ( 11.7 ) 59.3 ( 4.0 ) 52.2 ( 12.1 ) 49.2 ( 11.7 ) 55.3 ( 10.1 ) 54.9 ( 10.7 ) 49 ( 0 ) -
    Gender categorical
    Female subjects have been enrolled in the study.
    Units: Subjects
        Female
    		 6 8 3 42 21 3 32 1 115
    Subject analysis sets

    Subject analysis set title
    Full Analysis Set
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All participants were included in the full analysis set

    Subject analysis sets values
    		 Full Analysis Set
    Number of subjects
    115
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    93
        From 65-84 years
    22
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    53.0 ( 11.6 )
    Gender categorical
    Female subjects have been enrolled in the study.
    Units: Subjects
        Female
    115

    End points

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    End points reporting groups
    Reporting group title
    Part 1 Dose Escalation Cohort 1
    Reporting group description
    		 ZEN003694 48 mg PO QD with Talazoparib 1 mg PO QD in 28-day cycles. Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in the US and EU.

    Reporting group title
    Part 1 Dose Escalation Cohort 2
    Reporting group description
    		 ZEN003694 48 mg PO QD with Talazoparib 0.75 mg PO QD in 28-day cycles. Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in the US and EU.

    Reporting group title
    Part 1 Dose Escalation Cohort 3
    Reporting group description
    		 ZEN003694 36 mg PO QD with Talazoparib 1 mg PO QD in 28-day cycles. Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in the US and EU.

    Reporting group title
    Part 2 Stages 1 and 2
    Reporting group description
    		 ZEN003694 48 mg PO QD with Talazoparib 0.75 mg PO QD in 28-day cycles. Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in the US and EU.

    Reporting group title
    Expansion Cohort A
    Reporting group description
    		 Combination Treatment in Post-TROP2-ADC Patients. ZEN003694 48 mg PO QD with Talazoparib 0.75 mg PO QD (RP2D) in 28-day cycles. Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in the US and EU.

    Reporting group title
    Expansion Cohort B - ZEN003694 Monotherapy
    Reporting group description
    		 ZEN003694 48 mg PO QD as monotherapy at the in 28-day cycles with the option to cross-over to combination treatment of ZEN003694 48 mg PO QD with 0.75 mg Talazoparib PO QD at the time of disease progression (but no sooner than after 6 weeks of monotherapy). Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in the US and EU.

    Reporting group title
    Expansion Cohort C
    Reporting group description
    		 Combination Treatment in TROP2-ADC-naïve patients. ZEN003694 48 mg PO QD with Talazoparib PO QD (RP2D) in 28-day cycles. Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in China only.

    Reporting group title
    Expansion Cohort B - Cross-over Combination
    Reporting group description
    		 Post cross-over to combination treatment of ZEN003694 48 mg PO QD with 0.75 mg Talazoparib PO QD at the time of disease progression (but no sooner than after 6 weeks of monotherapy). Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in the US and EU.

    Subject analysis set title
    Full Analysis Set
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All participants were included in the full analysis set

    Primary: Part 1: Number of Participants With Dose-limiting Toxicities (DLT)

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    End point title
    		 Part 1: Number of Participants With Dose-limiting Toxicities (DLT) [1] [2]
    End point description
    Determination of DLT will be made during the first 28 days of treatment (i.e., Cycle 1) in the dose escalation phase. A DLT is defined as a clinically significant AE or laboratory abnormality that is considered possibly, probably or definitely related to study drug.
    End point type
    Primary
    End point timeframe
    Cycle 1, Up to 1 month
    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: Trial was terminated, no statistical analysis performed.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Trial was terminated, no statistical analysis performed.
    End point values
    		 Part 1 Dose Escalation Cohort 1 Part 1 Dose Escalation Cohort 2 Part 1 Dose Escalation Cohort 3 Full Analysis Set
    Number of subjects analysed
    6
    8
    3
    17
    Units: Number of Participants with DLT
    2
    1
    0
    2
    No statistical analyses for this end point

    Primary: Incidence of Treatment-related Adverse Events (AE)

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    End point title
    		 Incidence of Treatment-related Adverse Events (AE) [3] [4]
    End point description
    Adverse events were collected in all participants. For an event to be recorded as an AE, the onset must occur during or after the patient's first exposure to study drug and no later than 30 days after the last study drug dose.
    End point type
    Primary
    End point timeframe
    Cycle 1 Day 1 to 30 days post last dose (each cycle is 28 days) up to 22 months
    Notes
    [3] - 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: Trial was terminated, no statistical analysis performed.
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Trial was terminated, no statistical analysis performed.
    End point values
    		 Part 1 Dose Escalation Cohort 1 Part 1 Dose Escalation Cohort 2 Part 1 Dose Escalation Cohort 3 Part 2 Stages 1 and 2 Expansion Cohort A Expansion Cohort C
    Number of subjects analysed
    6
    8
    3
    42
    21
    32
    Units: Count of Participants
        Treatment Related Adverse Events
    6
    8
    3
    41
    19
    32
        Treatment Related Serious Adverse Events
    2
    1
    0
    4
    1
    13
    No statistical analyses for this end point

    Primary: Clinical Benefit Rate (CBR)

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    End point title
    		 Clinical Benefit Rate (CBR) [5] [6]
    End point description
    Percentage of patients with a best overall response of confirmed complete response (CR), partial response (PR), or stable disease (SD ≥ 4 cycles) by RECIST v1.1. Parts 1 and 2, Expansion Cohorts A and C. Patients who have received at least 3 weeks of per-protocol treatment during Cycle 1, or <3 weeks of treatment in Cycle 1 because of a DLT, will comprise the Efficacy Population. Patients who were determined to be "unevaluable" during Cycle 1 by the Sponsor and Investigator will not be included in the Efficacy Population.
    End point type
    Primary
    End point timeframe
    From screening up to 18 months
    Notes
    [5] - 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: Trial was terminated, no statistical analysis performed.
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Trial was terminated, no statistical analysis performed.
    End point values
    		 Part 1 Dose Escalation Cohort 1 Part 1 Dose Escalation Cohort 2 Part 1 Dose Escalation Cohort 3 Part 2 Stages 1 and 2 Expansion Cohort A Expansion Cohort C
    Number of subjects analysed
    6
    6
    3
    37
    14
    18
    Units: % of Participants
        number (not applicable)
    33.3
    66.7
    33.3
    32.4
    0
    11.1
    No statistical analyses for this end point

    Primary: Overall Response Rate (ORR)

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    End point title
    		 Overall Response Rate (ORR) [7] [8]
    End point description
    Percentage of participants with a confirmed complete response (CR) or partial response (PR) by RECIST 1.1.
    End point type
    Primary
    End point timeframe
    From screening up to 18 months
    Notes
    [7] - 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: Trial was terminated, no statistical analysis performed.
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Trial was terminated, no statistical analysis performed.
    End point values
    		 Part 1 Dose Escalation Cohort 1 Part 1 Dose Escalation Cohort 2 Part 1 Dose Escalation Cohort 3 Part 2 Stages 1 and 2 Expansion Cohort A Expansion Cohort C
    Number of subjects analysed
    6
    6
    3
    37
    14
    18
    Units: %
        number (not applicable)
    33.3
    16.7
    33.3
    21.6
    0
    5.6
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Cycle 1 Day 1 to 30 days post last dose (each cycle is 28 days) up to 22 months.
    Adverse event reporting additional description
    Adverse events were collected in all participants. For an event to be recorded as an AE, the onset must occur during or after the patient's first exposure to study drug and no later than 30 days after the last study drug .
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.0
    Reporting groups
    Reporting group title
    Part 1 Dose Escalation: Cohort 1
    Reporting group description
    		 ZEN003694 48 mg PO QD with Talazoparib 1 mg PO QD in 28-day cycles. Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in the US and EU.

    Reporting group title
    Part 1 Dose Escalation: Cohort 2
    Reporting group description
    		 ZEN003694 48 mg PO QD with Talazoparib 0.75 mg PO QD in 28-day cycles. Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in the US and EU.

    Reporting group title
    Part 1 Dose Escalation: Cohort 3
    Reporting group description
    		 ZEN003694 48 mg PO QD with Talazoparib 0.75 mg PO QD in 28-day cycles. Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in the US and EU.

    Reporting group title
    Part 2 Stages 1 and 2
    Reporting group description
    		 ZEN003694 48 mg PO QD with Talazoparib 0.75 mg PO QD in 28-day cycles. Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in the US and EU.

    Reporting group title
    Expansion Cohort A
    Reporting group description
    		 Combination Treatment in Post-TROP2-ADC Patients. ZEN003694 48 mg PO QD with Talazoparib 0.75 mg PO QD (RP2D) in 28-day cycles. Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2.

    Reporting group title
    Expansion Cohort B - Monotherapy
    Reporting group description
    		 ZEN003694 48 mg PO QD as monotherapy at the in 28-day cycles with the option to cross-over to combination treatment of ZEN003694 48 mg PO QD with 0.75 mg Talazoparib PO QD at the time of disease progression (but no sooner than after 6 weeks of monotherapy). Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in the US and EU.

    Reporting group title
    Expansion Cohort B - Cross-over Combination
    Reporting group description
    		 Post cross-over to combination treatment of ZEN003694 48 mg PO QD with 0.75 mg Talazoparib PO QD at the time of disease progression (but no sooner than after 6 weeks of monotherapy). Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in the US and EU.

    Reporting group title
    Expansion Cohort C
    Reporting group description
    		 Combination Treatment in TROP2-ADC-naïve Patients. ZEN003694 48 mg PO QD with Talazoparib PO QD (RP2D) in 28-day cycles. Patients have histologically confirmed Triple Negative Breast Cancer and have no documented germline mutations of BRCA1 or BRCA2. Includes sites in China only.

    Serious adverse events
    		 Part 1 Dose Escalation: Cohort 1 Part 1 Dose Escalation: Cohort 2 Part 1 Dose Escalation: Cohort 3 Part 2 Stages 1 and 2 Expansion Cohort A Expansion Cohort B - Monotherapy Expansion Cohort B - Cross-over Combination Expansion Cohort C
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 6 (50.00%)
    2 / 8 (25.00%)
    1 / 3 (33.33%)
    11 / 42 (26.19%)
    10 / 21 (47.62%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    14 / 32 (43.75%)
         number of deaths (all causes)
    1
    0
    0
    5
    2
    0
    0
    5
         number of deaths resulting from adverse events
    1
    0
    0
    3
    1
    0
    0
    4
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Metastasis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Neoplasm progression
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Tumour pain
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 42 (0.00%)
    1 / 21 (4.76%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 42 (0.00%)
    1 / 21 (4.76%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Disease progression
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Fatigue
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gait disturbance
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 42 (2.38%)
    1 / 21 (4.76%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    2 / 32 (6.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    Reproductive system and breast disorders
    Abnormal uterine bleeding
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uterine haemorrhage
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 42 (0.00%)
    1 / 21 (4.76%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Atelectasis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 42 (0.00%)
    1 / 21 (4.76%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    3 / 42 (7.14%)
    3 / 21 (14.29%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 3
    0 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    1 / 42 (2.38%)
    2 / 21 (9.52%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 42 (0.00%)
    1 / 21 (4.76%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    7 / 32 (21.88%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    7 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    White blood cell count decreased
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac failure
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 42 (0.00%)
    1 / 21 (4.76%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Sinus node dysfunction
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Apraxia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 42 (0.00%)
    1 / 21 (4.76%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ataxia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 42 (2.38%)
    1 / 21 (4.76%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 42 (0.00%)
    1 / 21 (4.76%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal cord compression
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Status epilepticus
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Thrombocytopenia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    3 / 42 (7.14%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    3 / 3
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    1 / 3 (33.33%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    1 / 3 (33.33%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    2 / 32 (6.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatic failure
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 42 (0.00%)
    1 / 21 (4.76%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertransaminasaemia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Urinary retention
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Muscular weakness
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 42 (0.00%)
    2 / 21 (9.52%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 42 (0.00%)
    1 / 21 (4.76%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Infection
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 42 (0.00%)
    1 / 21 (4.76%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 42 (0.00%)
    1 / 21 (4.76%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hypokalaemia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 42 (2.38%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0.05%
    Non-serious adverse events
    		 Part 1 Dose Escalation: Cohort 1 Part 1 Dose Escalation: Cohort 2 Part 1 Dose Escalation: Cohort 3 Part 2 Stages 1 and 2 Expansion Cohort A Expansion Cohort B - Monotherapy Expansion Cohort B - Cross-over Combination Expansion Cohort C
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    6 / 6 (100.00%)
    8 / 8 (100.00%)
    3 / 3 (100.00%)
    42 / 42 (100.00%)
    21 / 21 (100.00%)
    2 / 3 (66.67%)
    1 / 1 (100.00%)
    32 / 32 (100.00%)
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 6 (0.00%)
    3 / 8 (37.50%)
    0 / 3 (0.00%)
    10 / 42 (23.81%)
    3 / 21 (14.29%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    13 / 32 (40.63%)
         occurrences all number
    0
    3
    0
    10
    3
    0
    0
    13
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 6 (16.67%)
    3 / 8 (37.50%)
    0 / 3 (0.00%)
    12 / 42 (28.57%)
    5 / 21 (23.81%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    13 / 32 (40.63%)
         occurrences all number
    1
    3
    0
    12
    5
    0
    0
    13
    Blood alkaline phosphatase increased
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    2 / 42 (4.76%)
    1 / 21 (4.76%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    1
    1
    0
    2
    1
    0
    0
    1
    Blood bilirubin increased
         subjects affected / exposed
    2 / 6 (33.33%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    2 / 42 (4.76%)
    1 / 21 (4.76%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    25 / 32 (78.13%)
         occurrences all number
    2
    0
    0
    2
    1
    0
    0
    25
    Blood creatinine increased
         subjects affected / exposed
    2 / 6 (33.33%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    5 / 42 (11.90%)
    1 / 21 (4.76%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    8 / 32 (25.00%)
         occurrences all number
    2
    1
    0
    5
    1
    0
    0
    8
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    2 / 42 (4.76%)
    4 / 21 (19.05%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    5 / 32 (15.63%)
         occurrences all number
    0
    0
    0
    2
    4
    0
    0
    5
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    2 / 42 (4.76%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    6 / 32 (18.75%)
         occurrences all number
    0
    1
    0
    2
    0
    0
    0
    6
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    1 / 3 (33.33%)
    6 / 42 (14.29%)
    3 / 21 (14.29%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    8 / 32 (25.00%)
         occurrences all number
    0
    0
    1
    6
    3
    0
    0
    8
    Neutrophil count decreased
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 8 (25.00%)
    0 / 3 (0.00%)
    4 / 42 (9.52%)
    2 / 21 (9.52%)
    0 / 3 (0.00%)
    1 / 1 (100.00%)
    12 / 32 (37.50%)
         occurrences all number
    0
    2
    0
    4
    2
    0
    1
    12
    Platelet count decreased
         subjects affected / exposed
    3 / 6 (50.00%)
    4 / 8 (50.00%)
    0 / 3 (0.00%)
    16 / 42 (38.10%)
    8 / 21 (38.10%)
    1 / 3 (33.33%)
    1 / 1 (100.00%)
    16 / 32 (50.00%)
         occurrences all number
    3
    4
    0
    16
    8
    1
    1
    16
    Weight decreased
         subjects affected / exposed
    2 / 6 (33.33%)
    1 / 8 (12.50%)
    1 / 3 (33.33%)
    2 / 42 (4.76%)
    1 / 21 (4.76%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    6 / 32 (18.75%)
         occurrences all number
    2
    1
    1
    2
    1
    0
    0
    6
    White blood cell count decreased
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    3 / 42 (7.14%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    12 / 32 (37.50%)
         occurrences all number
    1
    0
    0
    3
    0
    0
    0
    12
    Cardiac disorders
    Sinus tachycardia
         subjects affected / exposed
    2 / 6 (33.33%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 42 (0.00%)
    1 / 21 (4.76%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    2 / 32 (6.25%)
         occurrences all number
    2
    1
    0
    0
    1
    0
    0
    2
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    4 / 42 (9.52%)
    2 / 21 (9.52%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    3 / 32 (9.38%)
         occurrences all number
    0
    0
    0
    4
    2
    0
    0
    3
    Dysgeusia
         subjects affected / exposed
    2 / 6 (33.33%)
    1 / 8 (12.50%)
    1 / 3 (33.33%)
    9 / 42 (21.43%)
    5 / 21 (23.81%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    2
    1
    1
    9
    5
    0
    0
    1
    Headache
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    5 / 42 (11.90%)
    3 / 21 (14.29%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    4 / 32 (12.50%)
         occurrences all number
    1
    0
    0
    5
    3
    0
    0
    4
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 6 (33.33%)
    1 / 8 (12.50%)
    2 / 3 (66.67%)
    8 / 42 (19.05%)
    10 / 21 (47.62%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    16 / 32 (50.00%)
         occurrences all number
    2
    1
    2
    8
    10
    0
    0
    16
    Thrombocytopenia
         subjects affected / exposed
    3 / 6 (50.00%)
    1 / 8 (12.50%)
    1 / 3 (33.33%)
    8 / 42 (19.05%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    3
    1
    1
    8
    0
    0
    0
    1
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 8 (12.50%)
    1 / 3 (33.33%)
    4 / 42 (9.52%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    3 / 32 (9.38%)
         occurrences all number
    1
    1
    1
    4
    0
    0
    0
    3
    Fatigue
         subjects affected / exposed
    4 / 6 (66.67%)
    3 / 8 (37.50%)
    1 / 3 (33.33%)
    14 / 42 (33.33%)
    13 / 21 (61.90%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    7 / 32 (21.88%)
         occurrences all number
    4
    3
    1
    14
    13
    0
    0
    7
    Malaise
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    6 / 32 (18.75%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    6
    Pain
         subjects affected / exposed
    2 / 6 (33.33%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    4 / 42 (9.52%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    2
    0
    0
    4
    0
    0
    0
    1
    Pyrexia
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    2 / 42 (4.76%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    3 / 32 (9.38%)
         occurrences all number
    1
    1
    0
    2
    0
    0
    0
    3
    Eye disorders
    Dyschromatopsia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    4 / 42 (9.52%)
    1 / 21 (4.76%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    0
    0
    4
    1
    0
    0
    1
    Photophobia
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    3 / 42 (7.14%)
    2 / 21 (9.52%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    1
    1
    0
    3
    2
    0
    0
    1
    Photopsia
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 8 (12.50%)
    1 / 3 (33.33%)
    9 / 42 (21.43%)
    3 / 21 (14.29%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    2 / 32 (6.25%)
         occurrences all number
    1
    1
    1
    9
    3
    1
    0
    2
    Vision blurred
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    1 / 3 (33.33%)
    4 / 42 (9.52%)
    5 / 21 (23.81%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    7 / 32 (21.88%)
         occurrences all number
    0
    0
    1
    4
    5
    0
    0
    7
    Visual impairment
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    6 / 42 (14.29%)
    1 / 21 (4.76%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    1
    0
    6
    1
    0
    0
    1
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    2 / 6 (33.33%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    4 / 42 (9.52%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 32 (0.00%)
         occurrences all number
    2
    0
    0
    4
    0
    0
    0
    0
    Constipation
         subjects affected / exposed
    2 / 6 (33.33%)
    3 / 8 (37.50%)
    0 / 3 (0.00%)
    6 / 42 (14.29%)
    5 / 21 (23.81%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    6 / 32 (18.75%)
         occurrences all number
    2
    3
    0
    6
    5
    0
    0
    6
    Diarrhoea
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 8 (0.00%)
    1 / 3 (33.33%)
    6 / 42 (14.29%)
    2 / 21 (9.52%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    5 / 32 (15.63%)
         occurrences all number
    1
    0
    1
    6
    2
    1
    0
    5
    Dry mouth
         subjects affected / exposed
    2 / 6 (33.33%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    2 / 42 (4.76%)
    3 / 21 (14.29%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    3 / 32 (9.38%)
         occurrences all number
    2
    0
    0
    2
    3
    0
    0
    3
    Dysphagia
         subjects affected / exposed
    2 / 6 (33.33%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 42 (2.38%)
    1 / 21 (4.76%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    2
    0
    0
    1
    1
    0
    0
    1
    Nausea
         subjects affected / exposed
    3 / 6 (50.00%)
    5 / 8 (62.50%)
    0 / 3 (0.00%)
    19 / 42 (45.24%)
    11 / 21 (52.38%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    19 / 32 (59.38%)
         occurrences all number
    3
    5
    0
    19
    11
    0
    0
    19
    Vomiting
         subjects affected / exposed
    2 / 6 (33.33%)
    4 / 8 (50.00%)
    0 / 3 (0.00%)
    11 / 42 (26.19%)
    4 / 21 (19.05%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    13 / 32 (40.63%)
         occurrences all number
    2
    4
    0
    11
    4
    1
    0
    13
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 6 (16.67%)
    2 / 8 (25.00%)
    0 / 3 (0.00%)
    1 / 42 (2.38%)
    3 / 21 (14.29%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    5 / 32 (15.63%)
         occurrences all number
    1
    2
    0
    1
    3
    0
    0
    5
    Dyspnoea
         subjects affected / exposed
    3 / 6 (50.00%)
    2 / 8 (25.00%)
    0 / 3 (0.00%)
    5 / 42 (11.90%)
    3 / 21 (14.29%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    2 / 32 (6.25%)
         occurrences all number
    3
    2
    0
    5
    3
    0
    0
    2
    Pleural effusion
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    2 / 42 (4.76%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 32 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    3 / 42 (7.14%)
    2 / 21 (9.52%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    0
    0
    0
    3
    2
    0
    0
    1
    Insomnia
         subjects affected / exposed
    2 / 6 (33.33%)
    0 / 8 (0.00%)
    1 / 3 (33.33%)
    2 / 42 (4.76%)
    1 / 21 (4.76%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    3 / 32 (9.38%)
         occurrences all number
    2
    0
    1
    2
    1
    0
    0
    3
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    2 / 6 (33.33%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    4 / 42 (9.52%)
    2 / 21 (9.52%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 32 (0.00%)
         occurrences all number
    2
    0
    0
    4
    2
    0
    0
    0
    Back pain
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    5 / 42 (11.90%)
    5 / 21 (23.81%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    2 / 32 (6.25%)
         occurrences all number
    1
    0
    0
    5
    5
    0
    0
    2
    Pain in extremity
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    3 / 42 (7.14%)
    2 / 21 (9.52%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 32 (0.00%)
         occurrences all number
    0
    0
    0
    3
    2
    0
    0
    0
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    1 / 6 (16.67%)
    2 / 8 (25.00%)
    0 / 3 (0.00%)
    1 / 42 (2.38%)
    2 / 21 (9.52%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 32 (0.00%)
         occurrences all number
    1
    2
    0
    1
    2
    0
    0
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    3 / 6 (50.00%)
    3 / 8 (37.50%)
    1 / 3 (33.33%)
    11 / 42 (26.19%)
    7 / 21 (33.33%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    18 / 32 (56.25%)
         occurrences all number
    3
    3
    1
    11
    7
    0
    0
    18
    Hypercholesterolaemia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    5 / 32 (15.63%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    5
    Hyperglycaemia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    6 / 42 (14.29%)
    8 / 21 (38.10%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    19 / 32 (59.38%)
         occurrences all number
    1
    0
    0
    6
    8
    0
    0
    19
    Hyperkalaemia
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    2 / 42 (4.76%)
    1 / 21 (4.76%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    1
    1
    0
    2
    1
    0
    0
    1
    Hypermagnesaemia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 42 (2.38%)
    1 / 21 (4.76%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    4 / 32 (12.50%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    4
    Hyperphosphataemia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    2 / 42 (4.76%)
    2 / 21 (9.52%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    2 / 32 (6.25%)
         occurrences all number
    0
    0
    0
    2
    2
    0
    0
    2
    Hypertriglyceridaemia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    6 / 32 (18.75%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    6
    Hypoalbuminaemia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 42 (2.38%)
    3 / 21 (14.29%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    3 / 32 (9.38%)
         occurrences all number
    1
    0
    0
    1
    3
    0
    0
    3
    Hypocalcaemia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 42 (2.38%)
    4 / 21 (19.05%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    3 / 32 (9.38%)
         occurrences all number
    0
    0
    0
    1
    4
    0
    0
    3
    Hypochloraemia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 42 (0.00%)
    0 / 21 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    7 / 32 (21.88%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    7
    Hypokalaemia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    2 / 42 (4.76%)
    3 / 21 (14.29%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    10 / 32 (31.25%)
         occurrences all number
    1
    0
    0
    2
    3
    0
    0
    10
    Hyponatraemia
         subjects affected / exposed
    2 / 6 (33.33%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    2 / 42 (4.76%)
    5 / 21 (23.81%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    12 / 32 (37.50%)
         occurrences all number
    2
    1
    0
    2
    5
    0
    0
    12
    Hypophosphataemia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    3 / 42 (7.14%)
    2 / 21 (9.52%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    4 / 32 (12.50%)
         occurrences all number
    0
    0
    0
    3
    2
    0
    0
    4

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    18 Mar 2019
    Amendment 1: 18-March-2019 Updated ZEN003694 starting dose from 72mg to 48mg QD
    29 Apr 2019
    Amendment 2: 29-April-2019 Updated eligibility criteria
    17 Dec 2019
    Amendment 3: 17-December 2019 Update to eligibility criteria and DLT definition
    11 May 2020
    Amendment 4: 11-May-2020 Update to eligibility criteria and study assessments
    23 Feb 2022
    Amendment 5: 23-February-2022 Expand the study to up to 120 subjects
    26 May 2022
    Amendment 6: 26-May-2022 Update to eligibility criteria and study assessments

    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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    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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