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    Clinical Trial Results:
    A Modular Phase I/II, Open-label, Multicentre Study to Assess AZD4573 in Novel Combinations with Anti-cancer Agents in Patients with Advanced Haematological Malignancies

    Summary
    EudraCT number
    		 2020-001642-18
    Trial protocol
    		 IE   ES   FR   IT  
    Global end of trial date

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

    Trial information

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    Trial identification
    Sponsor protocol code
    D8230C00002
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04630756
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    AstraZeneca AB
    Sponsor organisation address
    Södertälje, Södertälje, Sweden, 15185
    Public contact
    Global Clinical Lead, AstraZeneca, +1 877-240-9479, information.center@astrazeneca.com
    Scientific contact
    Global Clinical Lead, AstraZeneca, +1 877-240-9479, information.center@astrazeneca.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
    Interim
    Date of interim/final analysis
    31 Dec 2024
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    31 Dec 2024
    Global end of trial reached?
    No
    General information about the trial
    Main objective of the trial
    To assess AZD4573 in novel combinations with anti-cancer agents in patients with advanced haematological malignancies.
    Protection of trial subjects
    This study was performed in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with ICH/GCP, applicable regulatory requirements and the AstraZeneca policy on Bioethics.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    17 Feb 2021
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 30 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 7
    Country: Number of subjects enrolled
    France: 4
    Country: Number of subjects enrolled
    Ireland: 2
    Country: Number of subjects enrolled
    Korea, Republic of: 5
    Country: Number of subjects enrolled
    Poland: 3
    Country: Number of subjects enrolled
    Spain: 1
    Country: Number of subjects enrolled
    United Kingdom: 1
    Country: Number of subjects enrolled
    United States: 17
    Worldwide total number of subjects
    40
    EEA total number of subjects
    10
    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)
    27
    From 65 to 84 years
    13
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 This study was conducted from 17 February 2021 to 08 September 2023. Module 1 was conducted at 17 study centers in 10 countries. Module 2 was conducted at 2 sites in the United States.

    Pre-assignment
    Screening details
    		 The screening period was 30 days for both parts of the study. Informed Consent Form was signed prior to screening procedures. All study assessments were performed as per the schedule of assessment. Participants who met the eligibility criteria were randomized to study intervention in addition to receiving background local standard of care therapy.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Module 1 Part A: AZD4573 9 mg + 100g acalabrutinib BID
    Arm description
    		 Participants received AZD4573 9 mg as Intravenous (IV) infusion once weekly with acalabrutinib 100 mg twice daily.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    AZD4573
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received AZD4573 9 mg as Intravenous (IV) infusion once weekly with acalabrutinib 100 mg twice daily.

    Investigational medicinal product name
    Acalabrutinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received AZD4573 9 mg as Intravenous (IV) infusion once weekly with acalabrutinib 100 mg twice daily.

    Arm title
    		 Module 1 Part B: AZD4573 12 mg + 100g acalabrutinib BID
    Arm description
    		 Participants received AZD4573 dose expansion to RP2D 12 mg as IV infusion once weekly with acalabrutinib 100 mg twice daily.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Acalabrutinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received AZD4573 dose expansion to RP2D 12 mg as IV infusion once weekly with acalabrutinib 100 mg twice daily.

    Investigational medicinal product name
    AZD4573
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received AZD4573 dose expansion to RP2D 12 mg as IV infusion once weekly with acalabrutinib 100 mg twice daily.

    Arm title
    		 Module 2 Period 1 + 2: AZD4573 12 mg monotherapy + combination
    Arm description
    		 Participants received AZD4573 12 mg monotherapy until progression and thereafter received a combination regimen of AZD4573 12 mg once weekly and acalabrutinib 100 mg twice daily.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Acalabrutinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received AZD4573 12 mg monotherapy until progression and thereafter received a combination regimen of AZD4573 12 mg once weekly and acalabrutinib 100 mg twice daily.

    Investigational medicinal product name
    AZD4573
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received AZD4573 12 mg monotherapy until progression and thereafter received a combination regimen of AZD4573 12 mg once weekly and acalabrutinib 100 mg twice daily.

    Number of subjects in period 1
    		Module 1 Part A: AZD4573 9 mg + 100g acalabrutinib BID Module 1 Part B: AZD4573 12 mg + 100g acalabrutinib BID Module 2 Period 1 + 2: AZD4573 12 mg monotherapy + combination
    Started
    9
    28
    3
    Completed
    8
    28
    3
    Not completed
    1
    0
    0
         Ongoing subjects in Post Trial Access Program
    1
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Module 1 Part A: AZD4573 9 mg + 100g acalabrutinib BID
    Reporting group description
    		 Participants received AZD4573 9 mg as Intravenous (IV) infusion once weekly with acalabrutinib 100 mg twice daily.

    Reporting group title
    Module 1 Part B: AZD4573 12 mg + 100g acalabrutinib BID
    Reporting group description
    		 Participants received AZD4573 dose expansion to RP2D 12 mg as IV infusion once weekly with acalabrutinib 100 mg twice daily.

    Reporting group title
    Module 2 Period 1 + 2: AZD4573 12 mg monotherapy + combination
    Reporting group description
    		 Participants received AZD4573 12 mg monotherapy until progression and thereafter received a combination regimen of AZD4573 12 mg once weekly and acalabrutinib 100 mg twice daily.

    Reporting group values
    		 Module 1 Part A: AZD4573 9 mg + 100g acalabrutinib BID Module 1 Part B: AZD4573 12 mg + 100g acalabrutinib BID Module 2 Period 1 + 2: AZD4573 12 mg monotherapy + combination Total
    Number of subjects
    		 9 28 3 40
    Age Categorical
    Units: Participants
        In utero
    		 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0
        Adults (18-64 years)
    		 7 17 3 27
        From 65-84 years
    		 2 11 0 13
        85 years and over
    		 0 0 0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 51.2 ( 18.72 ) 61.7 ( 9.52 ) 59.7 ( 2.63 ) -
    Gender Categorical
    Units: Participants
        Female
    		 4 10 0 14
        Male
    		 5 18 3 26
    Race/Ethnicity
    Units: Subjects
        Asian
    		 2 8 0 10
        White
    		 6 17 2 25
        Not Reported
    		 1 1 0 2
        Missing
    		 0 2 0 2
        Other
    		 0 0 1 1

    End points

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    End points reporting groups
    Reporting group title
    Module 1 Part A: AZD4573 9 mg + 100g acalabrutinib BID
    Reporting group description
    		 Participants received AZD4573 9 mg as Intravenous (IV) infusion once weekly with acalabrutinib 100 mg twice daily.

    Reporting group title
    Module 1 Part B: AZD4573 12 mg + 100g acalabrutinib BID
    Reporting group description
    		 Participants received AZD4573 dose expansion to RP2D 12 mg as IV infusion once weekly with acalabrutinib 100 mg twice daily.

    Reporting group title
    Module 2 Period 1 + 2: AZD4573 12 mg monotherapy + combination
    Reporting group description
    		 Participants received AZD4573 12 mg monotherapy until progression and thereafter received a combination regimen of AZD4573 12 mg once weekly and acalabrutinib 100 mg twice daily.

    Primary: Module 1: Number of participants with adverse events

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    End point title
    		 Module 1: Number of participants with adverse events [1] [2]
    End point description
    The safety and tolerability of AZD4573 in combination with acalabrutinib was assessed in the safety analysis set. The safety analysis set included all participants who received any amount of AZD4573 and/or acalabrutinib.
    End point type
    Primary
    End point timeframe
    From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
    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: The endpoint title is specific to the arms which are presented only. Participants in Module 2: Periods 1 and 2 were not assessed for this outcome measure. Hence, only the arms which are referenced in the title are presented per outcome measure.
    [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: The endpoint title is specific to the arms which are presented only. Participants in Module 2: Periods 1 and 2 were not assessed for this outcome measure. Hence, only the arms which are referenced in the title are presented per outcome measure.
    End point values
    		 Module 1 Part A: AZD4573 9 mg + 100g acalabrutinib BID Module 1 Part B: AZD4573 12 mg + 100g acalabrutinib BID
    Number of subjects analysed
    9
    28
    Units: Participants
        Any adverse event (AE)
    9
    28
        Any serious adverse event (SAE)
    4
    16
    No statistical analyses for this end point

    Primary: Module 1: Overall response rate (ORR) of AZD4573 in combination with acalabrutinib

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    End point title
    		 Module 1: Overall response rate (ORR) of AZD4573 in combination with acalabrutinib [3] [4]
    End point description
    Objective response rate (ORR), defined as the proportion of participants who have a tumour response (complete response [CR] and partial response [PR]) was assessed in the response evaluable analysis set. The response evaluable analysis set included participants dosed with AZD4573 or acalabrutinib with a baseline tumour assessment. Here, 999.999 indicates that the value was not calculated due to an insufficient number of participants with events.
    End point type
    Primary
    End point timeframe
    From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
    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: The endpoint title is specific to the arms which are presented only. Participants in Module 2: Periods 1 and 2 were not assessed for this outcome measure. Hence, only the arms which are referenced in the title are presented per outcome measure.
    [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: The endpoint title is specific to the arms which are presented only. Participants in Module 2: Periods 1 and 2 were not assessed for this outcome measure. Hence, only the arms which are referenced in the title are presented per outcome measure.
    End point values
    		 Module 1 Part A: AZD4573 9 mg + 100g acalabrutinib BID Module 1 Part B: AZD4573 12 mg + 100g acalabrutinib BID
    Number of subjects analysed
    9
    28
    Units: Percentage of participants with response
        number (confidence interval 95%)
    44.4 (13.7 to 78.8)
    50.0 (30.6 to 69.4)
    No statistical analyses for this end point

    Primary: Module 2: Number of participants with adverse events

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    End point title
    		 Module 2: Number of participants with adverse events [5] [6]
    End point description
    Assessed safety and confirmed the RP2D of AZD4573 monotherapy in MCL participants and assessed the safety and tolerability of AZD4573 in combination with acalabrutinib in participants administered AZD4573 monotherapy in the safety analysis set. The safety analysis set included all participants who received any amount of AZD4573 and/or acalabrutinib.
    End point type
    Primary
    End point timeframe
    From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
    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: The endpoint title is specific to the arms which are presented only. Participants in Module 2: Periods 1 and 2 were not assessed for this outcome measure. Hence, only the arms which are referenced in the title are presented per outcome measure.
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint title is specific to the arms which are presented only. Participants in Module 2: Periods 1 and 2 were not assessed for this outcome measure. Hence, only the arms which are referenced in the title are presented per outcome measure.
    End point values
    		 Module 2 Period 1 + 2: AZD4573 12 mg monotherapy + combination
    Number of subjects analysed
    3
    Units: Number of Participants
        Any AE
    3
        Any SAE
    1
    No statistical analyses for this end point

    Secondary: Module 1: Complete response (CR) rate

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    End point title
    		 Module 1: Complete response (CR) rate [7]
    End point description
    CR, defined as no detectable evidence of tumor, according to the revised response criteria for malignant lymphoma, was assessed in the response evaluable analysis set. The response evaluable analysis set included participants dosed with AZD4573 or acalabrutinib with a baseline tumour assessment. Here, 999.999 indicates that the value was not calculated due to an insufficient number of participants with events.
    End point type
    Secondary
    End point timeframe
    From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint title is specific to the arms which are presented only. Participants in Module 2: Periods 1 and 2 were not assessed for this outcome measure. Hence, only the arms which are referenced in the title are presented per outcome measure.
    End point values
    		 Module 1 Part A: AZD4573 9 mg + 100g acalabrutinib BID Module 1 Part B: AZD4573 12 mg + 100g acalabrutinib BID
    Number of subjects analysed
    9
    28
    Units: Percentage of participants with response
        number (confidence interval 95%)
    11.1 (0.3 to 48.2)
    21.4 (8.3 to 41.0)
    No statistical analyses for this end point

    Secondary: Module 1: Cmax of AZD4573

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    End point title
    		 Module 1: Cmax of AZD4573 [8]
    End point description
    Maximum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administered (Cmax) was measured in the pharmacokinetic analysis set. The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK. Here, 999.999 indicates that the value was not calculated due to an insufficient number of participants analyzed.
    End point type
    Secondary
    End point timeframe
    Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint title is specific to the arms which are presented only. Participants in Module 2: Periods 1 and 2 were not assessed for this outcome measure. Hence, only the arms which are referenced in the title are presented per outcome measure.
    End point values
    		 Module 1 Part A: AZD4573 9 mg + 100g acalabrutinib BID Module 1 Part B: AZD4573 12 mg + 100g acalabrutinib BID
    Number of subjects analysed
    9
    12
    Units: nanograms per milliliter (ng/mL)
    geometric mean (geometric coefficient of variation)
        Cycle 1 Week 1 Day 1 (n=9, 12)
    164.2 ( 469.0 )
    112.6 ( 70.20 )
        Cycle 1 Week 2 Day 1 (n=6, 11)
    235.7 ( 359.3 )
    185.3 ( 50.61 )
        Cycle 1 Week 3 Day 1 (n=8, 11)
    337.8 ( 194.3 )
    270.8 ( 38.61 )
        Cycle 2 Week 1 Day 1 (n=6, 9)
    643.1 ( 578.0 )
    294.6 ( 48.83 )
    No statistical analyses for this end point

    Secondary: Module 1: Overall survival (OS)

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    End point title
    		 Module 1: Overall survival (OS) [9]
    End point description
    OS, defined as the time from first dose until the date of death from any cause, was measured in the full analysis set. The full analysis set included all participants who received any amount of study intervention. Here, 999.999 indicates that the value was not calculated due to an insufficient number of participants with events.
    End point type
    Secondary
    End point timeframe
    From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint title is specific to the arms which are presented only. Participants in Module 2: Periods 1 and 2 were not assessed for this outcome measure. Hence, only the arms which are referenced in the title are presented per outcome measure.
    End point values
    		 Module 1 Part A: AZD4573 9 mg + 100g acalabrutinib BID Module 1 Part B: AZD4573 12 mg + 100g acalabrutinib BID
    Number of subjects analysed
    9
    28
    Units: Months
        median (confidence interval 95%)
    999.999 (3.52 to 999.999)
    8.8 (3.91 to 999.999)
    No statistical analyses for this end point

    Secondary: Module 1: Duration of response (DoR)

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    End point title
    		 Module 1: Duration of response (DoR) [10]
    End point description
    DoR, defined as the time from the first objective response of CR or PR to the time of documented disease progression or death due to any cause, whichever occurs first, was measured in the response evaluable analysis set. The response evaluable analysis set included participants dosed with AZD4573 or acalabrutinib with a baseline tumour assessment. Here, 999.999 indicates that the value was not calculated due to an insufficient number of participants with events.
    End point type
    Secondary
    End point timeframe
    From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint title is specific to the arms which are presented only. Participants in Module 2: Periods 1 and 2 were not assessed for this outcome measure. Hence, only the arms which are referenced in the title are presented per outcome measure.
    End point values
    		 Module 1 Part A: AZD4573 9 mg + 100g acalabrutinib BID Module 1 Part B: AZD4573 12 mg + 100g acalabrutinib BID
    Number of subjects analysed
    9
    28
    Units: Months
        median (confidence interval 95%)
    4.4 (4.1 to 999.999)
    3.3 (1.2 to 6.2)
    No statistical analyses for this end point

    Secondary: Module 1: Progression free survival (PFS)

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    End point title
    		 Module 1: Progression free survival (PFS) [11]
    End point description
    PFS, defined as the time from first dose date to documented disease progression, or death from any cause, whichever occurs first, was measured in the full analysis set. The full analysis set included all participants who received any amount of study intervention. Here, 999.999 indicates that the value was not calculated due to an insufficient number of participants with events.
    End point type
    Secondary
    End point timeframe
    From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint title is specific to the arms which are presented only. Participants in Module 2: Periods 1 and 2 were not assessed for this outcome measure. Hence, only the arms which are referenced in the title are presented per outcome measure.
    End point values
    		 Module 1 Part A: AZD4573 9 mg + 100g acalabrutinib BID Module 1 Part B: AZD4573 12 mg + 100g acalabrutinib BID
    Number of subjects analysed
    9
    28
    Units: Months
        median (confidence interval 95%)
    2.1 (0.30 to 6.44)
    2.8 (1.91 to 3.98)
    No statistical analyses for this end point

    Secondary: Module 1: Cmax of acalabrutinib

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    End point title
    		 Module 1: Cmax of acalabrutinib [12]
    End point description
    Maximum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administered (Cmax) was measured in the pharmacokinetic analysis set. The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK. Here, 999.999 indicates that the value was not calculated due to an insufficient number of participants analyzed.
    End point type
    Secondary
    End point timeframe
    Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint title is specific to the arms which are presented only. Participants in Module 2: Periods 1 and 2 were not assessed for this outcome measure. Hence, only the arms which are referenced in the title are presented per outcome measure.
    End point values
    		 Module 1 Part A: AZD4573 9 mg + 100g acalabrutinib BID Module 1 Part B: AZD4573 12 mg + 100g acalabrutinib BID
    Number of subjects analysed
    7
    12
    Units: nanograms per milliliter (ng/mL)
    geometric mean (geometric coefficient of variation)
        Cycle 1 Week 1 Day 1 (n=6, 11)
    219.9 ( 66.94 )
    306.1 ( 76.06 )
        Cycle 1 Week 2 Day 1 (n=6, 10)
    209.8 ( 45.79 )
    322.7 ( 95.53 )
        Cycle 1 Week 3 Day 1 (n=7, 10)
    232.1 ( 74.77 )
    274.2 ( 78.98 )
        Cycle 2 Week 1 Day 1 (n=5, 8)
    217.5 ( 100.8 )
    256.7 ( 67.75 )
    No statistical analyses for this end point

    Secondary: Module 1: Cmax of ACP-5862

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    End point title
    		 Module 1: Cmax of ACP-5862 [13]
    End point description
    Maximum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administered (Cmax) was measured in the pharmacokinetic analysis set. The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK. Here, 999.999 indicates that the value was not calculated due to an insufficient number of participants analyzed.
    End point type
    Secondary
    End point timeframe
    Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1
    Notes
    [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint title is specific to the arms which are presented only. Participants in Module 2: Periods 1 and 2 were not assessed for this outcome measure. Hence, only the arms which are referenced in the title are presented per outcome measure.
    End point values
    		 Module 1 Part A: AZD4573 9 mg + 100g acalabrutinib BID Module 1 Part B: AZD4573 12 mg + 100g acalabrutinib BID
    Number of subjects analysed
    7
    11
    Units: nanograms per milliliter (ng/mL)
    geometric mean (geometric coefficient of variation)
        Cycle 1 Week 1 Day 1 (n=6, 11)
    199.2 ( 129.3 )
    250.2 ( 78.12 )
        Cycle 1 Week 2 Day 1 (n=6, 10)
    382.1 ( 51.58 )
    288.0 ( 63.26 )
        Cycle 1 Week 3 Day 1 (n=7, 10)
    320.8 ( 35.92 )
    282.9 ( 55.76 )
        Cycle 2 Week 1 Day 1 (n=5, 8)
    304.6 ( 79.28 )
    251.8 ( 45.54 )
    No statistical analyses for this end point

    Secondary: Module 1: AUClast of acalabrutinib

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    End point title
    		 Module 1: AUClast of acalabrutinib [14]
    End point description
    The area under the plasma concentration time curve from zero to the time of the last measurable concentration (AUClast) was measured in the pharmacokinetic analysis set. The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK. Here, 999.999 indicates that the value was not calculated due to an insufficient number of participants analyzed.
    End point type
    Secondary
    End point timeframe
    Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint title is specific to the arms which are presented only. Participants in Module 2: Periods 1 and 2 were not assessed for this outcome measure. Hence, only the arms which are referenced in the title are presented per outcome measure.
    End point values
    		 Module 1 Part A: AZD4573 9 mg + 100g acalabrutinib BID Module 1 Part B: AZD4573 12 mg + 100g acalabrutinib BID
    Number of subjects analysed
    7
    11
    Units: time*nanogram per milliliter (h*ng/mL)
    geometric mean (geometric coefficient of variation)
        Cycle 1 Week 1 Day 1 (n=6, 11)
    493.9 ( 58.91 )
    631.4 ( 69.98 )
        Cycle 1 Week 2 Day 1 (n=6, 10)
    520.9 ( 46.04 )
    638.2 ( 81.66 )
        Cycle 1 Week 3 Day 1 (n=7, 10)
    475.9 ( 45.57 )
    570.7 ( 67.75 )
        Cycle 2 Week 1 Day 1 (n=5, 8)
    481.8 ( 58.39 )
    424.5 ( 162.8 )
    No statistical analyses for this end point

    Secondary: Module 1: AUClast of AZD4573

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    End point title
    		 Module 1: AUClast of AZD4573 [15]
    End point description
    The area under the plasma concentration time curve from zero to the time of the last measurable concentration (AUClast) was measured in the pharmacokinetic analysis set. The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK. Here, 999.999 indicates that the value was not calculated due to an insufficient number of participants analyzed.
    End point type
    Secondary
    End point timeframe
    Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1
    Notes
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint title is specific to the arms which are presented only. Participants in Module 2: Periods 1 and 2 were not assessed for this outcome measure. Hence, only the arms which are referenced in the title are presented per outcome measure.
    End point values
    		 Module 1 Part A: AZD4573 9 mg + 100g acalabrutinib BID Module 1 Part B: AZD4573 12 mg + 100g acalabrutinib BID
    Number of subjects analysed
    8
    12
    Units: time*nanogram per milliliter (h*ng/mL)
    geometric mean (geometric coefficient of variation)
        Cycle 1 Week 1 Day 1 (n=6, 12)
    532.9 ( 164.5 )
    561.3 ( 60.83 )
        Cycle 1 Week 2 Day 1 (n=6, 11)
    845.3 ( 134.8 )
    929.0 ( 55.85 )
        Cycle 1 Week 3 Day 1 (n=8, 11)
    1273 ( 127.7 )
    1697 ( 62.55 )
        Cycle 2 Week 1 Day 1 (n=6, 9)
    1939 ( 330.9 )
    1439 ( 90.63 )
    No statistical analyses for this end point

    Secondary: Module 1: AUClast of ACP-5862

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    End point title
    		 Module 1: AUClast of ACP-5862 [16]
    End point description
    The area under the plasma concentration time curve from zero to the time of the last measurable concentration (AUClast) was measured in the pharmacokinetic analysis set. The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK. Here, 999.999 indicates that the value was not calculated due to an insufficient number of participants analyzed.
    End point type
    Secondary
    End point timeframe
    Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1
    Notes
    [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint title is specific to the arms which are presented only. Participants in Module 2: Periods 1 and 2 were not assessed for this outcome measure. Hence, only the arms which are referenced in the title are presented per outcome measure.
    End point values
    		 Module 1 Part A: AZD4573 9 mg + 100g acalabrutinib BID Module 1 Part B: AZD4573 12 mg + 100g acalabrutinib BID
    Number of subjects analysed
    7
    11
    Units: time*nanogram per milliliter (h*ng/mL)
    geometric mean (geometric coefficient of variation)
        Cycle 1 Week 1 Day 1 (n=6, 11)
    673.9 ( 93.89 )
    870.8 ( 68.73 )
        Cycle 1 Week 2 Day 1 (n=6, 10)
    1173 ( 48.03 )
    1135 ( 54.95 )
        Cycle 1 Week 3 Day 1 (n=7, 10)
    1204 ( 36.24 )
    1093 ( 54.50 )
        Cycle 2 Week 1 Day 1 (n=5, 8)
    941.9 ( 102.5 )
    849.3 ( 60.56 )
    No statistical analyses for this end point

    Secondary: Module 1: AUCinf of AZD4573

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    End point title
    		 Module 1: AUCinf of AZD4573 [17]
    End point description
    The area under the plasma concentration time curve from zero extrapolated to infinity (AUCinf) was measured in the pharmacokinetic analysis set. The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK. Here, 999.999 indicates that the value was not calculated due to an insufficient number of participants analyzed.
    End point type
    Secondary
    End point timeframe
    Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1
    Notes
    [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint title is specific to the arms which are presented only. Participants in Module 2: Periods 1 and 2 were not assessed for this outcome measure. Hence, only the arms which are referenced in the title are presented per outcome measure.
    End point values
    		 Module 1 Part A: AZD4573 9 mg + 100g acalabrutinib BID Module 1 Part B: AZD4573 12 mg + 100g acalabrutinib BID
    Number of subjects analysed
    5
    9
    Units: h*ng/mL
    geometric mean (geometric coefficient of variation)
        Cycle 1 Week 1 Day 1 (n=1, 4)
    999.999 ( 999.999 )
    640.5 ( 15.33 )
        Cycle 1 Week 2 Day 1 (n=4, 6)
    1188 ( 160.1 )
    847.4 ( 68.22 )
        Cycle 1 Week 3 Day 1 (n=5, 9)
    1588 ( 169.6 )
    1736 ( 67.09 )
        Cycle 2 Week 1 Day 1 (n=4, 5)
    4672 ( 162.9 )
    1853 ( 29.55 )
    No statistical analyses for this end point

    Secondary: Module 1: AUCinf of acalabrutinib

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    End point title
    		 Module 1: AUCinf of acalabrutinib [18]
    End point description
    The area under the plasma concentration time curve from zero extrapolated to infinity (AUCinf) was measured in the pharmacokinetic analysis set. The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK. Here, 999.999 indicates that the value was not calculated due to an insufficient number of participants analyzed.
    End point type
    Secondary
    End point timeframe
    Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1
    Notes
    [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint title is specific to the arms which are presented only. Participants in Module 2: Periods 1 and 2 were not assessed for this outcome measure. Hence, only the arms which are referenced in the title are presented per outcome measure.
    End point values
    		 Module 1 Part A: AZD4573 9 mg + 100g acalabrutinib BID Module 1 Part B: AZD4573 12 mg + 100g acalabrutinib BID
    Number of subjects analysed
    3
    5
    Units: h*ng/mL
    geometric mean (geometric coefficient of variation)
        Cycle 1 Week 1 Day 1 (n=3, 5)
    600.1 ( 34.99 )
    501.3 ( 58.03 )
        Cycle 1 Week 2 Day 1 (n=0, 0)
    999.999 ( 999.999 )
    999.999 ( 999.999 )
        Cycle 1 Week 3 Day 1 (n=0, 0)
    999.999 ( 999.999 )
    999.999 ( 999.999 )
        Cycle 2 Week 1 Day 1 (n=0, 0)
    999.999 ( 999.999 )
    999.999 ( 999.999 )
    No statistical analyses for this end point

    Secondary: Module 1: AUCinf of ACP-5862

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    End point title
    		 Module 1: AUCinf of ACP-5862 [19]
    End point description
    The area under the plasma concentration time curve from zero extrapolated to infinity (AUCinf) was measured in the pharmacokinetic analysis set. The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK. Here, 999.999 indicates that the value was not calculated due to an insufficient number of participants analyzed.
    End point type
    Secondary
    End point timeframe
    Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1
    Notes
    [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint title is specific to the arms which are presented only. Participants in Module 2: Periods 1 and 2 were not assessed for this outcome measure. Hence, only the arms which are referenced in the title are presented per outcome measure.
    End point values
    		 Module 1 Part A: AZD4573 9 mg + 100g acalabrutinib BID Module 1 Part B: AZD4573 12 mg + 100g acalabrutinib BID
    Number of subjects analysed
    2
    4
    Units: h*ng/mL
    geometric mean (geometric coefficient of variation)
        Cycle 1 Week 1 Day 1 (n=2, 4)
    999.999 ( 999.999 )
    935.2 ( 38.81 )
        Cycle 1 Week 2 Day 1 (n=0, 0)
    999.999 ( 999.999 )
    999.999 ( 999.999 )
        Cycle 1 Week 3 Day 1 (n=0, 0)
    999.999 ( 999.999 )
    999.999 ( 999.999 )
        Cycle 2 Week 1 Day 1 (n=0, 0)
    999.999 ( 999.999 )
    999.999 ( 999.999 )
    No statistical analyses for this end point

    Secondary: Module 1: tmax of AZD4573

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    End point title
    		 Module 1: tmax of AZD4573 [20]
    End point description
    The time to reach peak or maximum observed concentration following drug administration (tmax) was measured in the pharmacokinetic analysis set. The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK.
    End point type
    Secondary
    End point timeframe
    Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1
    Notes
    [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint title is specific to the arms which are presented only. Participants in Module 2: Periods 1 and 2 were not assessed for this outcome measure. Hence, only the arms which are referenced in the title are presented per outcome measure.
    End point values
    		 Module 1 Part A: AZD4573 9 mg + 100g acalabrutinib BID Module 1 Part B: AZD4573 12 mg + 100g acalabrutinib BID
    Number of subjects analysed
    8
    12
    Units: Hours (h)
    median (full range (min-max))
        Cycle 1 Week 1 Day 1 (n=6, 12)
    1.992 (0.750 to 4.17)
    2.083 (1.00 to 10.5)
        Cycle 1 Week 2 Day 1 (n=6, 11)
    1.892 (1.00 to 3.00)
    2.033 (1.05 to 2.15)
        Cycle 1 Week 3 Day 1 (n=8, 11)
    2.192 (0.933 to 3.32)
    2.000 (1.03 to 2.15)
        Cycle 2 Week 1 Day 1 (n=6, 9)
    2.067 (1.00 to 2.22)
    2.083 (1.85 to 3.63)
    No statistical analyses for this end point

    Secondary: Module 1: tmax of acalabrutinib

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    End point title
    		 Module 1: tmax of acalabrutinib [21]
    End point description
    The time to reach peak or maximum observed concentration following drug administration (tmax) was measured in the pharmacokinetic analysis set. The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK. Here, 999.999 indicates that the value was not calculated due to an insufficient number of participants analyzed.
    End point type
    Secondary
    End point timeframe
    Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1
    Notes
    [21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint title is specific to the arms which are presented only. Participants in Module 2: Periods 1 and 2 were not assessed for this outcome measure. Hence, only the arms which are referenced in the title are presented per outcome measure.
    End point values
    		 Module 1 Part A: AZD4573 9 mg + 100g acalabrutinib BID Module 1 Part B: AZD4573 12 mg + 100g acalabrutinib BID
    Number of subjects analysed
    7
    11
    Units: Hours (h)
    median (full range (min-max))
        Cycle 1 Week 1 Day 1 (n=6, 11)
    1.242 (1.02 to 3.80)
    1.117 (0.933 to 2.65)
        Cycle 1 Week 2 Day 1 (n=6, 9)
    2.017 (1.00 to 4.52)
    1.133 (0.950 to 11.6)
        Cycle 1 Week 3 Day 1 (n=7, 10)
    1.233 (1.00 to 3.17)
    1.433 (0.850 to 4.00)
        Cycle 2 Week 1 Day 1 (n=5, 7)
    1.933 (1.03 to 5.75)
    1.200 (0.833 to 2.25)
    No statistical analyses for this end point

    Secondary: Module 1: tmax of ACP-5862

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    End point title
    		 Module 1: tmax of ACP-5862 [22]
    End point description
    The time to reach peak or maximum observed concentration following drug administration (tmax) was measured in the pharmacokinetic analysis set. The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK. Here, 999.999 indicates that the value was not calculated due to an insufficient number of participants analyzed.
    End point type
    Secondary
    End point timeframe
    Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1
    Notes
    [22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint title is specific to the arms which are presented only. Participants in Module 2: Periods 1 and 2 were not assessed for this outcome measure. Hence, only the arms which are referenced in the title are presented per outcome measure.
    End point values
    		 Module 1 Part A: AZD4573 9 mg + 100g acalabrutinib BID Module 1 Part B: AZD4573 12 mg + 100g acalabrutinib BID
    Number of subjects analysed
    7
    11
    Units: Hours (h)
    median (full range (min-max))
        Cycle 1 Week 1 Day 1 (n=6, 11)
    3.067 (1.02 to 7.00)
    1.117 (0.933 to 7.08)
        Cycle 1 Week 2 Day 1 (n=6, 9)
    2.075 (1.08 to 7.52)
    2.117 (1.05 to 11.6)
        Cycle 1 Week 3 Day 1 (n=7, 10)
    1.233 (1.00 to 4.58)
    1.892 (0.850 to 4.00)
        Cycle 2 Week 1 Day 1 (n=5, 7)
    2.167 (2.05 to 8.92)
    2.117 (0.917 to 4.13)
    No statistical analyses for this end point

    Secondary: Module 1: t1/2 of AZD4573

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    End point title
    		 Module 1: t1/2 of AZD4573 [23]
    End point description
    The time taken for half the initial dose of drug administered to be eliminated from the body (t1/2) was measured in the pharmacokinetic analysis set. The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK. Here, 999.999 indicates that the value was not calculated due to an insufficient number of participants analyzed.
    End point type
    Secondary
    End point timeframe
    Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1
    Notes
    [23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint title is specific to the arms which are presented only. Participants in Module 2: Periods 1 and 2 were not assessed for this outcome measure. Hence, only the arms which are referenced in the title are presented per outcome measure.
    End point values
    		 Module 1 Part A: AZD4573 9 mg + 100g acalabrutinib BID Module 1 Part B: AZD4573 12 mg + 100g acalabrutinib BID
    Number of subjects analysed
    5
    10
    Units: Hours (h)
    geometric mean (geometric coefficient of variation)
        Cycle 1 Week 1 Day 1 (n=1, 5)
    999.999 ( 999.999 )
    3.692 ( 37.98 )
        Cycle 1 Week 2 Day 1 (n=4, 7)
    3.364 ( 43.80 )
    5.407 ( 73.47 )
        Cycle 1 Week 3 Day 1 (n=5, 10)
    4.465 ( 42.28 )
    6.177 ( 30.16 )
        Cycle 2 Week 1 Day 1 (n=4, 5)
    6.508 ( 30.61 )
    5.808 ( 25.52 )
    No statistical analyses for this end point

    Secondary: Module 1: t1/2 of acalabrutinib

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    End point title
    		 Module 1: t1/2 of acalabrutinib [24]
    End point description
    The time taken for half the initial dose of drug administered to be eliminated from the body (t1/2) was measured in the pharmacokinetic analysis set. The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK. Here, 999.999 indicates that the value was not calculated due to an insufficient number of participants analyzed.
    End point type
    Secondary
    End point timeframe
    Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1
    Notes
    [24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint title is specific to the arms which are presented only. Participants in Module 2: Periods 1 and 2 were not assessed for this outcome measure. Hence, only the arms which are referenced in the title are presented per outcome measure.
    End point values
    		 Module 1 Part A: AZD4573 9 mg + 100g acalabrutinib BID Module 1 Part B: AZD4573 12 mg + 100g acalabrutinib BID
    Number of subjects analysed
    6
    6
    Units: Hours (h)
    geometric mean (geometric coefficient of variation)
        Cycle 1 Week 1 Day 1 (n=3, 5)
    1.332 ( 22.01 )
    1.108 ( 12.06 )
        Cycle 1 Week 2 Day 1 (n=3, 6)
    1.383 ( 49.15 )
    1.274 ( 25.09 )
        Cycle 1 Week 3 Day 1 (n=6, 6)
    1.238 ( 20.93 )
    1.546 ( 38.08 )
        Cycle 2 Week 1 Day 1 (n=2, 4)
    999.999 ( 999.999 )
    1.398 ( 32.20 )
    No statistical analyses for this end point

    Secondary: Module 1: t1/2 of ACP-5862

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    End point title
    		 Module 1: t1/2 of ACP-5862 [25]
    End point description
    The time taken for half the initial dose of drug administered to be eliminated from the body (t1/2) was measured in the pharmacokinetic analysis set. The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK. Here, 999.999 indicates that the value was not calculated due to an insufficient number of participants analyzed.
    End point type
    Secondary
    End point timeframe
    Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1
    Notes
    [25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint title is specific to the arms which are presented only. Participants in Module 2: Periods 1 and 2 were not assessed for this outcome measure. Hence, only the arms which are referenced in the title are presented per outcome measure.
    End point values
    		 Module 1 Part A: AZD4573 9 mg + 100g acalabrutinib BID Module 1 Part B: AZD4573 12 mg + 100g acalabrutinib BID
    Number of subjects analysed
    5
    6
    Units: Hours (h)
    geometric mean (geometric coefficient of variation)
        Cycle 1 Week 1 Day 1 (n=2, 5)
    999.999 ( 999.999 )
    2.568 ( 33.27 )
        Cycle 1 Week 2 Day 1 (n=2, 4)
    999.999 ( 999.999 )
    3.021 ( 47.65 )
        Cycle 1 Week 3 Day 1 (n=5, 6)
    2.650 ( 34.68 )
    3.557 ( 38.06 )
        Cycle 2 Week 1 Day 1 (n=0, 2)
    999.999 ( 999.999 )
    999.999 ( 999.999 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.0
    Reporting groups
    Reporting group title
    Module 1 Part A: AZD4573 9 mg + 100g acalabrutinib BID
    Reporting group description
    		 Participants received AZD4573 9 mg as Intravenous (IV) infusion once weekly with acalabrutinib 100 mg twice daily.

    Reporting group title
    Module 1 Part B: AZD4573 12 mg + 100g acalabrutinib BID
    Reporting group description
    		 Participants received AZD4573 dose expansion to RP2D 12 mg as IV infusion once weekly with acalabrutinib 100 mg twice daily.

    Reporting group title
    Module 2 Period 1 + 2: AZD4573 12 mg monotherapy + combination
    Reporting group description
    		 Participants received AZD4573 12 mg monotherapy until progression and thereafter received a combination regimen of AZD4573 12 mg once weekly and acalabrutinib 100 mg twice daily.

    Serious adverse events
    		 Module 1 Part A: AZD4573 9 mg + 100g acalabrutinib BID Module 1 Part B: AZD4573 12 mg + 100g acalabrutinib BID Module 2 Period 1 + 2: AZD4573 12 mg monotherapy + combination
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 9 (44.44%)
    16 / 28 (57.14%)
    2 / 3 (66.67%)
         number of deaths (all causes)
    4
    16
    0
         number of deaths resulting from adverse events
    0
    2
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour pain
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 28 (3.57%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metastatic neoplasm
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 28 (3.57%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 28 (3.57%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood bilirubin increased
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 28 (3.57%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 28 (3.57%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood creatinine increased
         subjects affected / exposed
    0 / 9 (0.00%)
    2 / 28 (7.14%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic enzyme increased
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 28 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Liver function test abnormal
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 28 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Presyncope
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 28 (3.57%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 28 (3.57%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 28 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    0 / 9 (0.00%)
    2 / 28 (7.14%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 28 (3.57%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 28 (3.57%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Hypogammaglobulinaemia
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 28 (3.57%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 28 (3.57%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 28 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 28 (3.57%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 28 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 28 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infective exacerbation of chronic obstructive airways disease
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 28 (3.57%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 9 (0.00%)
    1 / 28 (3.57%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatitis B reactivation
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 28 (0.00%)
    1 / 3 (33.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia adenoviral
    alternative dictionary used: MedDRA v26.0
         subjects affected / exposed
    0 / 9 (0.00%)
    4 / 28 (14.29%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COVID-19 virus test
         subjects affected / exposed
    0 / 9 (0.00%)
    2 / 28 (7.14%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Module 1 Part A: AZD4573 9 mg + 100g acalabrutinib BID Module 1 Part B: AZD4573 12 mg + 100g acalabrutinib BID Module 2 Period 1 + 2: AZD4573 12 mg monotherapy + combination
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    9 / 9 (100.00%)
    28 / 28 (100.00%)
    3 / 3 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Lip neoplasm benign
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 28 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    Vascular disorders
    Orthostatic hypotension
         subjects affected / exposed
    1 / 9 (11.11%)
    1 / 28 (3.57%)
    0 / 3 (0.00%)
         occurrences all number
    1
    1
    0
    Hypotension
         subjects affected / exposed
    0 / 9 (0.00%)
    4 / 28 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    0
    4
    0
    Deep vein thrombosis
         subjects affected / exposed
    0 / 9 (0.00%)
    2 / 28 (7.14%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    General disorders and administration site conditions
    Chest discomfort
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 28 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    1
    Pyrexia
         subjects affected / exposed
    0 / 9 (0.00%)
    6 / 28 (21.43%)
    2 / 3 (66.67%)
         occurrences all number
    0
    6
    2
    Peripheral swelling
         subjects affected / exposed
    0 / 9 (0.00%)
    2 / 28 (7.14%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    Oedema peripheral
         subjects affected / exposed
    3 / 9 (33.33%)
    2 / 28 (7.14%)
    0 / 3 (0.00%)
         occurrences all number
    3
    2
    0
    Injection site erythema
         subjects affected / exposed
    1 / 9 (11.11%)
    1 / 28 (3.57%)
    0 / 3 (0.00%)
         occurrences all number
    1
    1
    0
    Fatigue
         subjects affected / exposed
    2 / 9 (22.22%)
    11 / 28 (39.29%)
    2 / 3 (66.67%)
         occurrences all number
    3
    12
    2
    Device related thrombosis
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 28 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    Catheter site related reaction
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 28 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    Catheter site erythema
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 28 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    Asthenia
         subjects affected / exposed
    1 / 9 (11.11%)
    2 / 28 (7.14%)
    0 / 3 (0.00%)
         occurrences all number
    1
    2
    0
    Application site erosion
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 28 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Hypoxia
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 28 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    1
    Rhinorrhea
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 28 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    Oropharyngeal pain
         subjects affected / exposed
    2 / 9 (22.22%)
    0 / 28 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    0
    Nasal congestion
         subjects affected / exposed
    0 / 9 (0.00%)
    3 / 28 (10.71%)
    0 / 3 (0.00%)
         occurrences all number
    0
    3
    0
    Hiccups
         subjects affected / exposed
    1 / 9 (11.11%)
    1 / 28 (3.57%)
    0 / 3 (0.00%)
         occurrences all number
    1
    1
    0
    Epistaxis
         subjects affected / exposed
    0 / 9 (0.00%)
    2 / 28 (7.14%)
    1 / 3 (33.33%)
         occurrences all number
    0
    2
    1
    Dyspnoea
         subjects affected / exposed
    0 / 9 (0.00%)
    5 / 28 (17.86%)
    2 / 3 (66.67%)
         occurrences all number
    0
    5
    2
    Cough
         subjects affected / exposed
    1 / 9 (11.11%)
    4 / 28 (14.29%)
    1 / 3 (33.33%)
         occurrences all number
    2
    6
    1
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    1 / 9 (11.11%)
    3 / 28 (10.71%)
    0 / 3 (0.00%)
         occurrences all number
    1
    3
    0
    Investigations
    Aspartate aminotransferase increased
         subjects affected / exposed
    3 / 9 (33.33%)
    15 / 28 (53.57%)
    0 / 3 (0.00%)
         occurrences all number
    12
    55
    0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 28 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    Blood bilirubin increased
         subjects affected / exposed
    1 / 9 (11.11%)
    3 / 28 (10.71%)
    0 / 3 (0.00%)
         occurrences all number
    1
    5
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    3 / 9 (33.33%)
    15 / 28 (53.57%)
    0 / 3 (0.00%)
         occurrences all number
    6
    46
    0
    Amylase increased
         subjects affected / exposed
    0 / 9 (0.00%)
    2 / 28 (7.14%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    Transaminases increased
         subjects affected / exposed
    1 / 9 (11.11%)
    1 / 28 (3.57%)
    0 / 3 (0.00%)
         occurrences all number
    2
    1
    0
    Weight increased
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 28 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    Lipase increased
         subjects affected / exposed
    1 / 9 (11.11%)
    1 / 28 (3.57%)
    0 / 3 (0.00%)
         occurrences all number
    2
    1
    0
    Blood creatinine increased
         subjects affected / exposed
    1 / 9 (11.11%)
    4 / 28 (14.29%)
    1 / 3 (33.33%)
         occurrences all number
    1
    5
    2
    Fibrin D dimer increased
         subjects affected / exposed
    1 / 9 (11.11%)
    1 / 28 (3.57%)
    0 / 3 (0.00%)
         occurrences all number
    2
    1
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    2 / 9 (22.22%)
    3 / 28 (10.71%)
    0 / 3 (0.00%)
         occurrences all number
    3
    6
    0
    White blood cell count decreased
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 28 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    1
    Hepatic enzyme increased
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 28 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    0
    Glutamate dehydrogenase increased
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 28 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    1 / 9 (11.11%)
    5 / 28 (17.86%)
    0 / 3 (0.00%)
         occurrences all number
    2
    6
    0
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    0 / 9 (0.00%)
    2 / 28 (7.14%)
    1 / 3 (33.33%)
         occurrences all number
    0
    2
    1
    Atrial fibrillation
         subjects affected / exposed
    0 / 9 (0.00%)
    2 / 28 (7.14%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    1 / 9 (11.11%)
    5 / 28 (17.86%)
    0 / 3 (0.00%)
         occurrences all number
    1
    7
    0
    Dizziness postural
         subjects affected / exposed
    1 / 9 (11.11%)
    1 / 28 (3.57%)
    0 / 3 (0.00%)
         occurrences all number
    1
    1
    0
    Headache
         subjects affected / exposed
    1 / 9 (11.11%)
    6 / 28 (21.43%)
    1 / 3 (33.33%)
         occurrences all number
    1
    8
    1
    Peripheral sensory neuropathy
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 28 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    0
    Presyncope
         subjects affected / exposed
    0 / 9 (0.00%)
    3 / 28 (10.71%)
    0 / 3 (0.00%)
         occurrences all number
    0
    4
    0
    Blood and lymphatic system disorders
    Thrombocytopenia
         subjects affected / exposed
    6 / 9 (66.67%)
    16 / 28 (57.14%)
    1 / 3 (33.33%)
         occurrences all number
    11
    46
    3
    Neutropenia
         subjects affected / exposed
    9 / 9 (100.00%)
    25 / 28 (89.29%)
    3 / 3 (100.00%)
         occurrences all number
    86
    126
    6
    Lymphopenia
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 28 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    Leukopenia
         subjects affected / exposed
    3 / 9 (33.33%)
    2 / 28 (7.14%)
    0 / 3 (0.00%)
         occurrences all number
    3
    2
    0
    Anaemia
         subjects affected / exposed
    3 / 9 (33.33%)
    14 / 28 (50.00%)
    1 / 3 (33.33%)
         occurrences all number
    3
    23
    1
    Ear and labyrinth disorders
    Deafness
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 28 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    Eye disorders
    Punctate keratitis
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 28 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    Scintillating scotoma
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 28 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    2 / 9 (22.22%)
    2 / 28 (7.14%)
    2 / 3 (66.67%)
         occurrences all number
    2
    2
    2
    Abdominal distension
         subjects affected / exposed
    1 / 9 (11.11%)
    1 / 28 (3.57%)
    1 / 3 (33.33%)
         occurrences all number
    1
    1
    1
    Abdominal discomfort
         subjects affected / exposed
    1 / 9 (11.11%)
    1 / 28 (3.57%)
    0 / 3 (0.00%)
         occurrences all number
    1
    1
    0
    Abdominal pain upper
         subjects affected / exposed
    1 / 9 (11.11%)
    1 / 28 (3.57%)
    0 / 3 (0.00%)
         occurrences all number
    1
    1
    0
    Dry mouth
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 28 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    1
    Abdominal pain lower
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 28 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    1
    Vomiting
         subjects affected / exposed
    1 / 9 (11.11%)
    11 / 28 (39.29%)
    1 / 3 (33.33%)
         occurrences all number
    1
    19
    1
    Saliva altered
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 28 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    Nausea
         subjects affected / exposed
    4 / 9 (44.44%)
    19 / 28 (67.86%)
    2 / 3 (66.67%)
         occurrences all number
    7
    33
    2
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 9 (0.00%)
    4 / 28 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    0
    4
    0
    Epigastric discomfort
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 28 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    Dysphagia
         subjects affected / exposed
    0 / 9 (0.00%)
    2 / 28 (7.14%)
    1 / 3 (33.33%)
         occurrences all number
    0
    3
    1
    Dyspepsia
         subjects affected / exposed
    1 / 9 (11.11%)
    1 / 28 (3.57%)
    0 / 3 (0.00%)
         occurrences all number
    1
    1
    0
    Diarrhoea
         subjects affected / exposed
    3 / 9 (33.33%)
    14 / 28 (50.00%)
    3 / 3 (100.00%)
         occurrences all number
    7
    32
    5
    Constipation
         subjects affected / exposed
    0 / 9 (0.00%)
    4 / 28 (14.29%)
    2 / 3 (66.67%)
         occurrences all number
    0
    4
    2
    Hepatobiliary disorders
    Hyperbilirubinaemia
         subjects affected / exposed
    0 / 9 (0.00%)
    3 / 28 (10.71%)
    0 / 3 (0.00%)
         occurrences all number
    0
    9
    0
    Skin and subcutaneous tissue disorders
    Rash macular
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 28 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    Night sweats
         subjects affected / exposed
    0 / 9 (0.00%)
    3 / 28 (10.71%)
    1 / 3 (33.33%)
         occurrences all number
    0
    4
    1
    Keratosis pilaris
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 28 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    Petechiae
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 28 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    1
    Rash maculo-papular
         subjects affected / exposed
    2 / 9 (22.22%)
    2 / 28 (7.14%)
    0 / 3 (0.00%)
         occurrences all number
    3
    2
    0
    Renal and urinary disorders
    Glycosuria
         subjects affected / exposed
    1 / 9 (11.11%)
    2 / 28 (7.14%)
    0 / 3 (0.00%)
         occurrences all number
    1
    3
    0
    Proteinuria
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 28 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    Musculoskeletal and connective tissue disorders
    Bone pain
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 28 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    1
    Pain in extremity
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 28 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    1
    Myalgia
         subjects affected / exposed
    2 / 9 (22.22%)
    1 / 28 (3.57%)
    0 / 3 (0.00%)
         occurrences all number
    2
    1
    0
    Muscle spasms
         subjects affected / exposed
    0 / 9 (0.00%)
    3 / 28 (10.71%)
    0 / 3 (0.00%)
         occurrences all number
    0
    3
    0
    Back pain
         subjects affected / exposed
    1 / 9 (11.11%)
    5 / 28 (17.86%)
    1 / 3 (33.33%)
         occurrences all number
    1
    5
    1
    Arthralgia
         subjects affected / exposed
    1 / 9 (11.11%)
    2 / 28 (7.14%)
    0 / 3 (0.00%)
         occurrences all number
    2
    3
    0
    Infections and infestations
    COVID-19
         subjects affected / exposed
    3 / 9 (33.33%)
    2 / 28 (7.14%)
    0 / 3 (0.00%)
         occurrences all number
    4
    2
    0
    Cellulitis
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 28 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    Escherichia urinary tract infection
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 28 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    1
    0
    1
    Fungal skin infection
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 28 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    0 / 9 (0.00%)
    2 / 28 (7.14%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    Oral candidiasis
         subjects affected / exposed
    0 / 9 (0.00%)
    2 / 28 (7.14%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    Oral herpes
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 28 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    Pharyngitis
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 28 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    Pneumonia
         subjects affected / exposed
    1 / 9 (11.11%)
    1 / 28 (3.57%)
    0 / 3 (0.00%)
         occurrences all number
    1
    1
    0
    Respiratory syncytial virus infection
         subjects affected / exposed
    0 / 9 (0.00%)
    2 / 28 (7.14%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    Rhinovirus infection
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 28 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    Diverticulitis
         subjects affected / exposed
    0 / 9 (0.00%)
    0 / 28 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    1
    Catheter site infection
         subjects affected / exposed
    1 / 9 (11.11%)
    0 / 28 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 9 (11.11%)
    4 / 28 (14.29%)
    1 / 3 (33.33%)
         occurrences all number
    1
    4
    1
    Dehydration
         subjects affected / exposed
    1 / 9 (11.11%)
    1 / 28 (3.57%)
    0 / 3 (0.00%)
         occurrences all number
    1
    1
    0
    Hyperglycaemia
         subjects affected / exposed
    0 / 9 (0.00%)
    3 / 28 (10.71%)
    0 / 3 (0.00%)
         occurrences all number
    0
    4
    0
    Hyperkalaemia
         subjects affected / exposed
    1 / 9 (11.11%)
    2 / 28 (7.14%)
    0 / 3 (0.00%)
         occurrences all number
    1
    2
    0
    Hyperphosphataemia
         subjects affected / exposed
    0 / 9 (0.00%)
    8 / 28 (28.57%)
    2 / 3 (66.67%)
         occurrences all number
    0
    9
    3
    Hypertriglyceridaemia
         subjects affected / exposed
    1 / 9 (11.11%)
    1 / 28 (3.57%)
    0 / 3 (0.00%)
         occurrences all number
    4
    4
    0
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 9 (0.00%)
    2 / 28 (7.14%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    Hypocalcaemia
         subjects affected / exposed
    0 / 9 (0.00%)
    4 / 28 (14.29%)
    0 / 3 (0.00%)
         occurrences all number
    0
    7
    0
    Hypokalaemia
         subjects affected / exposed
    0 / 9 (0.00%)
    8 / 28 (28.57%)
    0 / 3 (0.00%)
         occurrences all number
    0
    14
    0
    Hypomagnesaemia
         subjects affected / exposed
    0 / 9 (0.00%)
    2 / 28 (7.14%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    Hyponatraemia
         subjects affected / exposed
    1 / 9 (11.11%)
    1 / 28 (3.57%)
    0 / 3 (0.00%)
         occurrences all number
    1
    2
    0
    Hypophosphataemia
         subjects affected / exposed
    0 / 9 (0.00%)
    7 / 28 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    14
    0
    Tumour lysis syndrome
         subjects affected / exposed
    0 / 9 (0.00%)
    6 / 28 (21.43%)
    0 / 3 (0.00%)
         occurrences all number
    0
    13
    0

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    03 Jul 2020
    Amended core inclusion criteria to update calculated creatinine clearance from ≥ 50 mL/minute to ≥ 60 mL/minute, specify that participants should be able to swallow capsules and remove serum creatinine from criteria for adequate organ function; updated exclusion criteria regarding anticoagulant therapy; updated justification for dose; updated exclusion criteria regarding participants on anticoagulant therapy; updated DLT criteria for timing, febrile neutropenia and thrombocytopenia, and definition of isolated changes in GGT in DLT criteria exclusions; included warfarin or equivalent vitamin K antagonists to prohibited concomitant therapies; added requirement that acalabrutinib treatment must be discontinued if participants require vitamin K antagonist or combined administration of antiplatelet and therapeutic anticoagulation while on study; added additional safety monitoring and potential stopping criteria.
    21 Jul 2021
    Updated study design to include additional Module 2 AZD4573 monotherapy window followed by combination therapy with acalabrutinib; updated requirements for overnight hospitalization based on emerging data from ongoing FTIH study; updated exploratory objectives; amended Module 1 description to include MZL participants; changed data cut-off for primary analysis for each expansion subgroup from after all participants have had the opportunity to be followed for at least 12 months to at least 6 months; added clarification on TLS monitoring, updated study synopsis to reflect additional module and addition of participants with r/r MZL to Module 1.
    01 Aug 2022
    Updated core exclusion criteria: reduced CAR-T criteria to within 60 days prior to first dose of study drug; updated Module 1 part B: changed so that any safe dose level can be backfilled to approximately 21 patients instead of 12; removed Module 1 exclusion criteria for BTK inhibitors; updated schedule of activities to have less frequent assessments in earlier cycles; updated PHL process to reflect experience of AZD4573 liver safety profile.
    01 Jun 2023
    Updated overall study design to include rationale as to why study has permanently halted; added text throughout protocol to define that participants still receiving clinical benefit of treatment may continue to receive study treatment, initially planned interim analysis will not be performed, and Module 1 DLBCL cohorts will be pooled for the purpose of primary analysis; updated end of study definition in core section of the protocol.

    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.
    Due to the overall AZD4573 development programme being discontinued as part of a strategic portfolio decision, available data analyzed for this study is limited.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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