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    Clinical Trial Results:
    A Master Protocol Evaluating the Safety and Efficacy of Therapies for Metastatic Castration-resistant Prostate Cancer (mCRPC)

    Summary
    EudraCT number
    2020-001305-23
    Trial protocol
    DE   NL   SE   DK   IT  
    Global end of trial date
    23 Oct 2023

    Results information
    Results version number
    v1(current)
    This version publication date
    07 Nov 2024
    First version publication date
    07 Nov 2024
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    20190505
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT04631601
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Amgen Inc.
    Sponsor organisation address
    One Amgen Center Drive, Thousand Oaks, United States,
    Public contact
    Amgen (EUROPE) GmbH, Amgen Inc., MedInfoInternational@amgen.com
    Scientific contact
    Study Director, Amgen Inc., MedInfoInternational@amgen.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
    23 Oct 2023
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    23 Oct 2023
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The main objective was to evaluate the safety, tolerability and maximum tolerated dose or recommended phase 2 dose (RP2D) of acapatamab in combination with enzalutamide (Subprotocol A), acapatamab in combination with abiraterone (Subprotocol B), or acapatamab in combination with AMG 404 (Subprotocol C, Parts 1 and 2), evaluate preliminary antitumor activity of AMG monotherapy (Subprotocol C, Part 3) and to evaluate the safety and tolerability of acapatamab (Subprotocol D) in participants with mCRPC.
    Protection of trial subjects
    This study was conducted in accordance with the protocol and with: consensus ethical principles derived from international guidelines including the Declaration of Helsinki and Council for International Organizations of Medical Sciences International Ethical Guidelines, applicable International Council for Harmonisation (ICH) Good Clinical Practice (GCP) guidelines and applicable ICH laws and regulations.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    15 Jan 2021
    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
    United States: 24
    Country: Number of subjects enrolled
    Denmark: 5
    Country: Number of subjects enrolled
    Spain: 17
    Country: Number of subjects enrolled
    Sweden: 4
    Country: Number of subjects enrolled
    United Kingdom: 4
    Worldwide total number of subjects
    54
    EEA total number of subjects
    26
    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)
    16
    From 65 to 84 years
    38
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    54 participants were enrolled at 11 centers in Denmark, Spain, Sweden, the United Kingdom, and the United States between 15 January 2021 and 23 October 2023. One additional participant was enrolled in Subprotocol D. To protect participant privacy, the results of this participant are not included in this summary.

    Pre-assignment
    Screening details
    A total of 54 participants were enrolled and 53 received study treatment.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Subprotocol A: Acapatamab and Enzalutamide
    Arm description
    In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) extended intravenous (eIV) infusion, followed by the target dose (60-minute intravenous [IV] infusion) for the following doses throughout the first cycle. In subsequent cycles, participants received acapatamab at the target dose in 28-day cycles. Participants also received enzalutamide as oral tablets or oral capsules.
    Arm type
    Experimental

    Investigational medicinal product name
    Enzalutamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet, Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Enzalutamide was taken as either oral capsules or oral tablets.

    Investigational medicinal product name
    Acapatamab
    Investigational medicinal product code
    Other name
    AMG 160
    Pharmaceutical forms
    Powder for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Acapatamab was administered as a short-term or extended IV infusion.

    Arm title
    Subprotocol B: Acapatamab and Abiraterone
    Arm description
    In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) eIV infusion, followed by the target dose (60-minute IV infusion) for the following doses throughout the first cycle. In subsequent cycles, participants received acapatamab at the target dose in 28-day cycles. Participants also received abiraterone as oral tablets and prednisone (or prednisolone in some regions).
    Arm type
    Experimental

    Investigational medicinal product name
    Abiraterone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Abiraterone was taken as oral tablets.

    Investigational medicinal product name
    Acapatamab
    Investigational medicinal product code
    Other name
    AMG 160
    Pharmaceutical forms
    Powder for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Acapatamab was administered as a short-term or extended IV infusion.

    Arm title
    Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404
    Arm description
    In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) eIV infusion, followed by the target dose (60-minute IV infusion) for the following doses throughout the first cycle. In subsequent cycles (≥ 2), participants received acapatamab at the target dose in 28-day cycles. Participants also received abiraterone as oral tablets and prednisone (or prednisolone in some regions). Participants also received AMG 404 as a short-term 30 minute IV infusion once per cycle.
    Arm type
    Experimental

    Investigational medicinal product name
    AMG 404
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    AMG 404 was administered as a short-term IV infusion.

    Investigational medicinal product name
    Acapatamab
    Investigational medicinal product code
    Other name
    AMG 160
    Pharmaceutical forms
    Powder for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Acapatamab was administered as a short-term or extended IV infusion.

    Arm title
    Subprotocol C, Part 3: AMG 404 Monotherapy
    Arm description
    Participants received AMG 404 as a short-term 30-minute IV infusion once during each cycle.
    Arm type
    Experimental

    Investigational medicinal product name
    AMG 404
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    AMG 404 was administered as a short-term IV infusion.

    Number of subjects in period 1
    Subprotocol A: Acapatamab and Enzalutamide Subprotocol B: Acapatamab and Abiraterone Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404 Subprotocol C, Part 3: AMG 404 Monotherapy
    Started
    14
    15
    15
    10
    Received study treatment
    14
    14
    15
    10
    Completed
    1
    0
    2
    5
    Not completed
    13
    15
    13
    5
         Adverse event, serious fatal
    4
    5
    8
    2
         Consent withdrawn by subject
    2
    -
    -
    1
         Lost to follow-up
    -
    1
    -
    -
         Decision by sponsor
    7
    9
    5
    2

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Subprotocol A: Acapatamab and Enzalutamide
    Reporting group description
    In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) extended intravenous (eIV) infusion, followed by the target dose (60-minute intravenous [IV] infusion) for the following doses throughout the first cycle. In subsequent cycles, participants received acapatamab at the target dose in 28-day cycles. Participants also received enzalutamide as oral tablets or oral capsules.

    Reporting group title
    Subprotocol B: Acapatamab and Abiraterone
    Reporting group description
    In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) eIV infusion, followed by the target dose (60-minute IV infusion) for the following doses throughout the first cycle. In subsequent cycles, participants received acapatamab at the target dose in 28-day cycles. Participants also received abiraterone as oral tablets and prednisone (or prednisolone in some regions).

    Reporting group title
    Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404
    Reporting group description
    In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) eIV infusion, followed by the target dose (60-minute IV infusion) for the following doses throughout the first cycle. In subsequent cycles (≥ 2), participants received acapatamab at the target dose in 28-day cycles. Participants also received abiraterone as oral tablets and prednisone (or prednisolone in some regions). Participants also received AMG 404 as a short-term 30 minute IV infusion once per cycle.

    Reporting group title
    Subprotocol C, Part 3: AMG 404 Monotherapy
    Reporting group description
    Participants received AMG 404 as a short-term 30-minute IV infusion once during each cycle.

    Reporting group values
    Subprotocol A: Acapatamab and Enzalutamide Subprotocol B: Acapatamab and Abiraterone Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404 Subprotocol C, Part 3: AMG 404 Monotherapy Total
    Number of subjects
    14 15 15 10 54
    Age Categorical
    Units: Subjects
        Adults (18-64 years)
    3 7 4 2 16
        From 65-84 years
    11 8 11 8 38
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    68.43 ( 4.83 ) 64.5 ( 8.6 ) 68.47 ( 9.33 ) 64.40 ( 9.94 ) -
    Gender Categorical
    Units: Subjects
        Female
    0 0 0 0 0
        Male
    14 15 15 10 54
    Ethnicity
    Units: Subjects
        Hispanic/Latino
    0 2 0 0 2
        Not Hispanic/Latino
    14 13 15 10 52
    Race
    Units: Subjects
        Asian
    0 0 1 0 1
        Black or African American
    0 0 0 1 1
        White
    14 14 14 9 51
        Other
    0 1 0 0 1

    End points

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    End points reporting groups
    Reporting group title
    Subprotocol A: Acapatamab and Enzalutamide
    Reporting group description
    In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) extended intravenous (eIV) infusion, followed by the target dose (60-minute intravenous [IV] infusion) for the following doses throughout the first cycle. In subsequent cycles, participants received acapatamab at the target dose in 28-day cycles. Participants also received enzalutamide as oral tablets or oral capsules.

    Reporting group title
    Subprotocol B: Acapatamab and Abiraterone
    Reporting group description
    In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) eIV infusion, followed by the target dose (60-minute IV infusion) for the following doses throughout the first cycle. In subsequent cycles, participants received acapatamab at the target dose in 28-day cycles. Participants also received abiraterone as oral tablets and prednisone (or prednisolone in some regions).

    Reporting group title
    Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404
    Reporting group description
    In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) eIV infusion, followed by the target dose (60-minute IV infusion) for the following doses throughout the first cycle. In subsequent cycles (≥ 2), participants received acapatamab at the target dose in 28-day cycles. Participants also received abiraterone as oral tablets and prednisone (or prednisolone in some regions). Participants also received AMG 404 as a short-term 30 minute IV infusion once per cycle.

    Reporting group title
    Subprotocol C, Part 3: AMG 404 Monotherapy
    Reporting group description
    Participants received AMG 404 as a short-term 30-minute IV infusion once during each cycle.

    Subject analysis set title
    Subprotocol A (Cohort 1a): Acapatamab and Enzalutamide
    Subject analysis set type
    Full analysis
    Subject analysis set description
    In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) eIV infusion, followed by the target dose (60-minute IV infusion) for the following doses throughout the first cycle. In subsequent cycles, participants received acapatamab at the target dose in 28-day cycles. Participants also received enzalutamide as oral tablets or oral capsules.

    Subject analysis set title
    Subprotocol A (Cohort 1b): Acapatamab and Enzalutamide
    Subject analysis set type
    Full analysis
    Subject analysis set description
    In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) eIV infusion, followed by the target dose (60-minute IV infusion) for the following doses throughout the first cycle. In subsequent cycles, participants received acapatamab at the target dose in 28-day cycles. Participants also received enzalutamide as oral tablets or oral capsules.

    Subject analysis set title
    Subprotocol A (Cohort 2a): Acapatamab and Enzalutamide
    Subject analysis set type
    Full analysis
    Subject analysis set description
    In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) eIV infusion, followed by the target dose (60-minute IV infusion) for the following doses throughout the first cycle. In subsequent cycles, participants received acapatamab at the target dose in 28-day cycles. Participants also received enzalutamide as oral tablets or oral capsules.

    Subject analysis set title
    Subprotocol A (Cohort 2b): Acapatamab and Enzalutamide
    Subject analysis set type
    Full analysis
    Subject analysis set description
    In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) eIV infusion, followed by the target dose (60-minute IV infusion) for the following doses throughout the first cycle. In subsequent cycles, participants received acapatamab at the target dose in 28-day cycles. Participants also received enzalutamide as oral tablets or oral capsules.

    Subject analysis set title
    Subprotocol B (Cohort 1): Acapatamab and Abiraterone
    Subject analysis set type
    Full analysis
    Subject analysis set description
    In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) eIV infusion, followed by the target dose (60-minute IV infusion) for the following doses throughout the first cycle. In subsequent cycles, participants received acapatamab at the target dose in 28-day cycles. Participants also received abiraterone as oral tablets and prednisone (or prednisolone in some regions).

    Subject analysis set title
    Subprotocol B (Cohort 2): Acapatamab and Abiraterone
    Subject analysis set type
    Full analysis
    Subject analysis set description
    In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) eIV infusion, followed by the target dose (60-minute IV infusion) for the following doses throughout the first cycle. In subsequent cycles, participants received acapatamab at the target dose in 28-day cycles. Participants also received abiraterone as oral tablets and prednisone (or prednisolone in some regions).

    Subject analysis set title
    Subprotocol B (Cohort 2, Expansion): Acapatamab & Abiraterone
    Subject analysis set type
    Full analysis
    Subject analysis set description
    In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) eIV infusion, followed by the target dose (60-minute IV infusion) for the following doses throughout the first cycle. In subsequent cycles, participants received acapatamab at the target dose in 28-day cycles. Participants also received abiraterone as oral tablets and prednisone (or prednisolone in some regions).

    Subject analysis set title
    Subprotocol C, Parts 1 & 2 (Exploration): Acapatamab & AMG 404
    Subject analysis set type
    Full analysis
    Subject analysis set description
    In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) eIV infusion, followed by the target dose (60-minute IV infusion) for the following doses throughout the first cycle. In subsequent cycles (≥ 2), participants received acapatamab at the target dose in 28-day cycles. Participants also received abiraterone as oral tablets and prednisone (or prednisolone in some regions). Participants also received AMG 404 as a short-term 30 minute IV infusion once per cycle.

    Subject analysis set title
    Subprotocol C, Parts 1 & 2 (Expansion): Acapatamab & AMG 404
    Subject analysis set type
    Full analysis
    Subject analysis set description
    In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) eIV infusion, followed by the target dose (60-minute IV infusion) for the following doses throughout the first cycle. In subsequent cycles (≥ 2), participants received acapatamab at the target dose in 28-day cycles. Participants also received abiraterone as oral tablets and prednisone (or prednisolone in some regions). Participants also received AMG 404 as a short-term 30 minute IV infusion once per cycle.

    Primary: Subprotocols A, B and C (Parts 1 and 2): Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)

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    End point title
    Subprotocols A, B and C (Parts 1 and 2): Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) [1] [2]
    End point description
    DLTs were defined as any adverse event (per Common Terminology Criteria for Adverse Events (CTCAE) v5: Grade 5=Death, Grade 4=Life-threatening, Grade 3=Moderate) occurring within 28 days of the first AMG 160 dose, possibly related to the treatment, including: - Grade 5 toxicity - Grade 4 thrombocytopenia - Grade 3 thrombocytopenia with significant hemorrhage - Grade 4 neutropenia > 5 days - Febrile neutropenia - Grade 3 anemia requiring transfusion - Grade ≥3 non-hematologic toxicity (with exceptions per protocol) - Aspartate transaminase/alanine transaminase >3x upper limit of normal (ULN) with serum total bilirubin >2x ULN without cholestasis or another clear cause - Grade ≥3 non-hematological toxicity delaying treatment > 2 weeks or resulting in <75% dose administration DLT Analysis Set: Included all participants who received at least one AMG 160 dose and had an evaluable DLT endpoint (had a DLT or completed all planned doses without a DLT within 28-day DLT window in Cycle 1).
    End point type
    Primary
    End point timeframe
    Day 1 to Day 28
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analyses were pre-planned for this endpoint.
    [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: No statistical analyses were pre-planned for this endpoint.
    End point values
    Subprotocol A: Acapatamab and Enzalutamide Subprotocol B: Acapatamab and Abiraterone Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404
    Number of subjects analysed
    14
    13
    15
    Units: participants
    3
    1
    6
    No statistical analyses for this end point

    Primary: Subprotocols A, B and C (Parts 1 and 2): Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)

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    End point title
    Subprotocols A, B and C (Parts 1 and 2): Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) [3] [4]
    End point description
    A TEAE was defined as any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment that started after the first dose of acapatamab, or AMG 404 (subprotocol C, parts 1 and 2), whichever was earlier. A treatment-related TEAE was defined as a TEAE that had a reasonable possibility of being caused by acapatamab, or AMG 404 (subprotocol C, parts 1 and 2 only). Clinically significant changes from baseline in vital signs and clinical laboratory tests were also recorded as TEAEs. Safety Analysis Set: Included all participants who were enrolled and received at least 1 dose of acapatamab, or AMG 404 (subprotocol C, parts 1 and 2 only).
    End point type
    Primary
    End point timeframe
    From first dose of acapatamab/AMG 404 to the first of 30 days after last dose of acapatamab/AMG404, end of study date or the initiation of a new anticancer therapy (up to a maximum of 3 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: No statistical analyses were pre-planned for this endpoint.
    [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: No statistical analyses were pre-planned for this endpoint.
    End point values
    Subprotocol A: Acapatamab and Enzalutamide Subprotocol B: Acapatamab and Abiraterone Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404
    Number of subjects analysed
    14
    14
    15
    Units: participants
        At least 1 TEAE
    14
    14
    15
        At least 1 treatment-related TEAE
    14
    14
    15
    No statistical analyses for this end point

    Primary: Subprotocol C, Part 3: Objective Response Rate (ORR)

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    End point title
    Subprotocol C, Part 3: Objective Response Rate (ORR) [5] [6]
    End point description
    ORR was defined as the percentage of participants who experienced a complete response (CR) or partial response (PR), per response evaluation criteria in solid tumors (RECIST) 1.1 with Prostate Cancer Working Group 3 (PCWG3) modifications. Responses were required to be confirmed at least 4 weeks later. RECIST Evaluable Analysis Set: Included all participants that were enrolled and received at least 1 dose of AMG 404 and had measurable baseline disease per RECIST 1.1 and had the opportunity to be followed for at least 9 weeks starting from study Day 1.
    End point type
    Primary
    End point timeframe
    From Cycle 1 Day 1 until progression, start of new anticancer therapy, or up to 3 years after the first dose of AMG 404 (each cycle was 28 days, maximum duration of AMG 404 treatment was 105.1 weeks).
    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: No statistical analyses were pre-planned for this endpoint.
    [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: No statistical analyses were pre-planned for this endpoint.
    End point values
    Subprotocol C, Part 3: AMG 404 Monotherapy
    Number of subjects analysed
    6
    Units: percentage of participants
        number (confidence interval 95%)
    0 (0.00 to 45.93)
    No statistical analyses for this end point

    Primary: Subprotocol C, Part 3: Percentage of Participants Who Experienced a Circulating Tumor Cell 0 (CTC0) Response

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    End point title
    Subprotocol C, Part 3: Percentage of Participants Who Experienced a Circulating Tumor Cell 0 (CTC0) Response [7] [8]
    End point description
    CTC0 response was defined as CTC0 (reduction of CTCs > 0 to 0 at any post-baseline measurement). The baseline was defined as the last non-missing value on or prior to the pre-dose of AMG 404 assessments on Cycle 1 Day 1. CTC0 Evaluable Analysis Set: Included all participants that were enrolled, received at least 1 dose of AMG 404 and had baseline CTC > 0.
    End point type
    Primary
    End point timeframe
    Cycle 1 Day 1 to 14 days post-last dose of AMG 404 (each cycle was 28 days, maximum duration of AMG 404 treatment was 105.1 weeks).
    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: No statistical analyses were pre-planned for this endpoint.
    [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: No statistical analyses were pre-planned for this endpoint.
    End point values
    Subprotocol C, Part 3: AMG 404 Monotherapy
    Number of subjects analysed
    5
    Units: percentage of participants
        number (confidence interval 95%)
    20.0 (0.51 to 71.64)
    No statistical analyses for this end point

    Primary: Subprotocol C, Part 3: Percentage of Participants Who Experienced a CTC Conversion Response

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    End point title
    Subprotocol C, Part 3: Percentage of Participants Who Experienced a CTC Conversion Response [9] [10]
    End point description
    CTC conversion response was defined as ≥ 5 CTCs/7.5 mL blood at baseline that converted to ≤ 4 CTCs/7.5 mL blood at any post-baseline measurement. The baseline was defined as the last non-missing value on or prior to the pre-dose assessments of AMG 404 on Cycle 1 Day 1. CTC Conversion Evaluable Analysis Set: Included all participants that were enrolled, received at least 1 dose of AMG 404 and had baseline CTC ≥ 5.
    End point type
    Primary
    End point timeframe
    Cycle 1 Day 1 to 14 days post-last dose of AMG 404 (each cycle was 28 days, maximum duration of AMG 404 treatment was 105.1 weeks).
    Notes
    [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analyses were pre-planned for this endpoint.
    [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: No statistical analyses were pre-planned for this endpoint.
    End point values
    Subprotocol C, Part 3: AMG 404 Monotherapy
    Number of subjects analysed
    3
    Units: percentage of participants
        number (confidence interval 95%)
    0.0 (0.00 to 70.76)
    No statistical analyses for this end point

    Primary: Subprotocol C, Part 3: Percentage of Participants Who Experienced a Prostate Specific Antigen (PSA) Response

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    End point title
    Subprotocol C, Part 3: Percentage of Participants Who Experienced a Prostate Specific Antigen (PSA) Response [11] [12]
    End point description
    A PSA response was defined as the below and must have been confirmed by a second consecutive value 3 weeks later: - PSA 30 response: ≥ 30% reduction from the baseline PSA. - PSA 50 response: ≥ 50% reduction from the baseline PSA. - PSA 70 response: ≥ 70% reduction from the baseline PSA. - PSA 90 response: ≥ 90% reduction from the baseline PSA. The baseline was defined as the last non-missing value on or prior to the pre-dose of AMG 404 assessments on Cycle 1 Day 1. PSA Response Evaluable Set: Included all participants that were enrolled, received at least 1 dose of AMG 404, had measurable (i.e., > 0) baseline PSA and had the opportunity to be followed for at least 9 weeks starting from study Day 1.
    End point type
    Primary
    End point timeframe
    Cycle 1 Day 1 to 5 months post-last dose of AMG 404 (each cycle was 28 days, maximum duration of AMG 404 treatment was 105.1 weeks).
    Notes
    [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analyses were pre-planned for this endpoint.
    [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: No statistical analyses were pre-planned for this endpoint.
    End point values
    Subprotocol C, Part 3: AMG 404 Monotherapy
    Number of subjects analysed
    10
    Units: percentage of participants
    number (confidence interval 95%)
        PSA 30 Response
    20.0 (2.52 to 55.61)
        PSA 50 Response
    20.0 (2.52 to 55.61)
        PSA 70 Response
    10.0 (0.25 to 44.50)
        PSA 90 Response
    10.0 (0.25 to 44.50)
    No statistical analyses for this end point

    Secondary: Subprotocols A. B and C (Parts 1 and 2): ORR

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    End point title
    Subprotocols A. B and C (Parts 1 and 2): ORR [13]
    End point description
    ORR was defined as the percentage of participants who experienced a CR or PR, per RECIST 1.1 with PCWG3 modifications. Responses were required to be confirmed at least 4 weeks later. RECIST 1.1 Evaluable Analysis Set: Included all participants that were enrolled, received at least 1 dose of AMG 160 and had measurable baseline disease per RECIST 1.1 per protocol and had the opportunity to be followed for at least 9 weeks starting from study Day 1.
    End point type
    Secondary
    End point timeframe
    From Cycle 1 Day 1 until progression, start of new anticancer therapy, or up to 3 years after the first dose of acapatamab/AMG 404 (each cycle was 28 days, maximum duration of acapatamab treatment was 98.4 weeks/AMG 404 treatment was 95.3 weeks).
    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: No statistical analyses were pre-planned for this endpoint.
    End point values
    Subprotocol A: Acapatamab and Enzalutamide Subprotocol B: Acapatamab and Abiraterone Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404
    Number of subjects analysed
    2
    5
    7
    Units: percentage of participants
        number (confidence interval 95%)
    50.0 (1.26 to 98.74)
    40.0 (5.27 to 85.34)
    14.3 (0.36 to 57.87)
    No statistical analyses for this end point

    Secondary: Subprotocols A, B and C (Parts 1 and 2): Percentage of Participants Who Experienced a CTC Conversion Response

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    End point title
    Subprotocols A, B and C (Parts 1 and 2): Percentage of Participants Who Experienced a CTC Conversion Response [14]
    End point description
    CTC conversion response was defined as ≥ 5 CTCs/7.5 mL blood at baseline that converted to ≤ 4 CTCs/7.5 mL blood at any post-baseline measurement. The baseline was defined as the last non-missing value on or prior to the pre-dose of acapatamab assessments on Cycle 1 Day 1. CTC Conversion Evaluable Analysis Set: Included all participants that were enrolled, received at least 1 dose of acapatamab/AMG 404 and had baseline CTC ≥ 5.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 to 14 days post-last dose of acapatamab/AMG 404 (each cycle was 28 days, maximum duration of acapatamab treatment was 98.4 weeks/AMG 404 treatment was 95.3 weeks).
    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: No statistical analyses were pre-planned for this endpoint.
    End point values
    Subprotocol A: Acapatamab and Enzalutamide Subprotocol B: Acapatamab and Abiraterone Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404
    Number of subjects analysed
    8
    5
    3
    Units: percentage of participants
        number (confidence interval 95%)
    75.0 (34.91 to 96.81)
    100.0 (47.82 to 100.00)
    66.7 (9.43 to 99.16)
    No statistical analyses for this end point

    Secondary: Subprotocols A, B and C (Parts 1 and 2): Percentage of Participants Who Experienced a CTC0 Response

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    End point title
    Subprotocols A, B and C (Parts 1 and 2): Percentage of Participants Who Experienced a CTC0 Response [15]
    End point description
    CTC0 response was defined as CTC0 (reduction of CTCs > 0 to 0 at any post-baseline measurement). The baseline was defined as the last non-missing value on or prior to the pre-dose of acapatamab assessments on Cycle 1 Day 1. CTC0 Evaluable Analysis Set: Included all participants that were enrolled, received at least 1 dose of acapatamab/AMG 404 and had baseline CTC > 0.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 to 14 days post-last dose of acapatamab/AMG 404 (each cycle was 28 days, maximum duration of acapatamab treatment was 98.4 weeks/AMG 404 treatment was 95.3 weeks).
    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: No statistical analyses were pre-planned for this endpoint.
    End point values
    Subprotocol A: Acapatamab and Enzalutamide Subprotocol B: Acapatamab and Abiraterone Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404
    Number of subjects analysed
    11
    6
    5
    Units: percentage of participants
        number (confidence interval 95%)
    63.6 (30.79 to 89.07)
    16.7 (0.42 to 64.12)
    60.0 (14.66 to 94.73)
    No statistical analyses for this end point

    Secondary: Subprotocols A, B and C (Parts 1 and 2): Percentage of Participants Who Experienced a PSA Response

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    End point title
    Subprotocols A, B and C (Parts 1 and 2): Percentage of Participants Who Experienced a PSA Response [16]
    End point description
    A PSA response was defined as the below and must have been confirmed by a second consecutive value 3 weeks later: - PSA 30 response: ≥ 30% reduction from the baseline PSA. - PSA 50 response: ≥ 50% reduction from the baseline PSA. - PSA 70 response: ≥ 70% reduction from the baseline PSA. - PSA 90 response: ≥ 90% reduction from the baseline PSA. The baseline was defined as the last non-missing value on or prior to the pre-dose of acapatamab assessments on Cycle 1 Day 1. PSA Response Evaluable Set: Included all participants that were enrolled, received at least 1 dose of acapatamab/AMG 404, had measurable (i.e., > 0) baseline PSA and had the opportunity to be followed for at least 9 weeks starting from study Day 1.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 to 5 months post-last dose of acapatamab/AMG 404 (each cycle was 28 days, maximum duration of acapatamab treatment was 98.4 weeks/AMG 404 treatment was 95.3 weeks).
    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: No statistical analyses were pre-planned for this endpoint.
    End point values
    Subprotocol A: Acapatamab and Enzalutamide Subprotocol B: Acapatamab and Abiraterone Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404
    Number of subjects analysed
    14
    14
    15
    Units: percentage of participants
    number (confidence interval 95%)
        PSA 30 Response
    71.4 (41.90 to 91.61)
    50.0 (23.04 to 76.96)
    33.3 (11.82 to 61.62)
        PSA 50 Response
    71.4 (41.90 to 91.61)
    42.9 (17.66 to 71.14)
    26.7 (7.79 to 55.10)
        PSA 70 Response
    64.3 (35.14 to 87.24)
    35.7 (12.76 to 64.86)
    20.0 (4.33 to 48.09)
        PSA 90 Response
    64.3 (35.14 to 87.24)
    21.4 (4.66 to 50.80)
    13.3 (1.66 to 40.46)
    No statistical analyses for this end point

    Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Duration of CTC0 Response

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    End point title
    Subprotocols A, B and C (Parts 1, 2 and 3): Duration of CTC0 Response
    End point description
    Duration of CTC0 response was defined as the time from the date of initial CTC0 response to the earlier of CTC0 progression or death. Participants who had not ended their response at the time of analysis had duration of CTC0 response censored on the date of their last CTC0 or CTC conversion assessment. Duration of CTC0 was not calculable due to too few responders. Calculation required > 10 responders to be accurate and meaningful.
    End point type
    Secondary
    End point timeframe
    From date of initial CTC0 response to the earlier of CTC0 progression or death (up to a maximum of 3 years).
    End point values
    Subprotocol A: Acapatamab and Enzalutamide Subprotocol B: Acapatamab and Abiraterone Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404 Subprotocol C, Part 3: AMG 404 Monotherapy
    Number of subjects analysed
    0 [17]
    0 [18]
    0 [19]
    0 [20]
    Units: months
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    ( to )
    Notes
    [17] - Duration of CTC0 response was not calculable.
    [18] - Duration of CTC0 response was not calculable.
    [19] - Duration of CTC0 response was not calculable.
    [20] - Duration of CTC0 response was not calculable.
    No statistical analyses for this end point

    Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Duration of PSA Response

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    End point title
    Subprotocols A, B and C (Parts 1, 2 and 3): Duration of PSA Response
    End point description
    Duration of PSA response was defined as the time of an initial PSA response (PSA 50) to the earlier of PSA progression or death. Participants who had not ended their response at the time of analysis had duration of PSA response censored on the date of their last PSA measurement. Duration of PSA response was not calculable due to too few responders. Calculation required > 10 responders to be accurate and meaningful.
    End point type
    Secondary
    End point timeframe
    From date of an initial PSA response (PSA 50) to the earlier of PSA progression or death (up to a maximum of 3 years).
    End point values
    Subprotocol A: Acapatamab and Enzalutamide Subprotocol B: Acapatamab and Abiraterone Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404 Subprotocol C, Part 3: AMG 404 Monotherapy
    Number of subjects analysed
    0 [21]
    0 [22]
    0 [23]
    0 [24]
    Units: months
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    ( to )
    Notes
    [21] - Duration of PSA response was not calculable.
    [22] - Duration of PSA response was not calculable.
    [23] - Duration of PSA response was not calculable.
    [24] - Duration of PSA response was not calculable.
    No statistical analyses for this end point

    Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Duration of CTC Conversion Response

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    End point title
    Subprotocols A, B and C (Parts 1, 2 and 3): Duration of CTC Conversion Response
    End point description
    Duration of CTC conversion response was defined as the time from the date of an initial CTC conversion response to the earlier of CTC conversion progression or death. Participants who had not ended their response at the time of analysis had duration of CTC response censored on the date of their last CTC0 or CTC conversion assessment. Duration of CTC conversion response was not calculable due to too few responders. Calculation required > 10 responders to be accurate and meaningful.
    End point type
    Secondary
    End point timeframe
    From the date of an initial CTC conversion response to the earlier of CTC conversion progression or death (up to a maximum of 3 years).
    End point values
    Subprotocol A: Acapatamab and Enzalutamide Subprotocol B: Acapatamab and Abiraterone Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404 Subprotocol C, Part 3: AMG 404 Monotherapy
    Number of subjects analysed
    0 [25]
    0 [26]
    0 [27]
    0 [28]
    Units: months
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    ( to )
    Notes
    [25] - Duration of CTC conversion response was not calculable.
    [26] - Duration of CTC conversion response was not calculable.
    [27] - Duration of CTC conversion response was not calculable.
    [28] - Duration of CTC conversion response was not calculable.
    No statistical analyses for this end point

    Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Duration of Response per RECIST 1.1

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    End point title
    Subprotocols A, B and C (Parts 1, 2 and 3): Duration of Response per RECIST 1.1
    End point description
    Duration of response per RECIST 1.1 was defined as the time from the date of an initial objective response (CR/PR) per RECIST 1.1 to the earlier of soft-tissue progression per RECIST 1.1 or death. CR/PR must have been confirmed at least 4 weeks later. Participants who had not ended their response at the time of analysis had duration of response censored at their last evaluable tumor assessment by computed tomography (CT)/magnetic resonance imaging (MRI) scan. Duration of response was not calculable due to too few responders. Calculation required > 10 responders to be accurate and meaningful.
    End point type
    Secondary
    End point timeframe
    From date of an initial objective response per RECIST 1.1 to the earlier of soft-tissue progression per RECIST 1.1 or death (up to a maximum of 3 years).
    End point values
    Subprotocol A: Acapatamab and Enzalutamide Subprotocol B: Acapatamab and Abiraterone Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404 Subprotocol C, Part 3: AMG 404 Monotherapy
    Number of subjects analysed
    0 [29]
    0 [30]
    0 [31]
    0 [32]
    Units: months
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    ( to )
    Notes
    [29] - Duration of response was not calculable.
    [30] - Duration of response was not calculable.
    [31] - Duration of response was not calculable.
    [32] - Duration of response was not calculable.
    No statistical analyses for this end point

    Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Radiographic Progression Free Survival (rPFS)

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    End point title
    Subprotocols A, B and C (Parts 1, 2 and 3): Radiographic Progression Free Survival (rPFS)
    End point description
    rPFS was defined as the interval from study Day 1 to the earlier of a radiographic progression or death from any cause; otherwise, rPFS was censored at the last evaluable tumor assessment date. If a participant had no post-baseline radiographic tumor assessment and a vital status of alive or known, rPFS was censored at study Day 1. The median was estimated using the Kaplan-Meier method and the 95% confidence interval was estimated using the method by Brookmeyer and Crowley. 9999 = median and upper limit not calculable due to fewer than 50% events. Lower bound was calculated from observed data that was available (25% percentile). 99999 = upper limit was not calculable due to low number of events. Safety Analysis Set: Included all participants who were enrolled and received at least 1 dose of acapatamab or AMG 404 (Subprotocol C only).
    End point type
    Secondary
    End point timeframe
    From study Day 1 to the earlier of a radiographic progression or death from any cause (up to a maximum of 3 years).
    End point values
    Subprotocol A: Acapatamab and Enzalutamide Subprotocol B: Acapatamab and Abiraterone Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404 Subprotocol C, Part 3: AMG 404 Monotherapy
    Number of subjects analysed
    14
    14
    15
    10
    Units: months
        median (confidence interval 95%)
    18.20 (10.97 to 99999)
    8.51 (3.71 to 99999)
    9999 (2.00 to 9999)
    3.48 (1.61 to 99999)
    No statistical analyses for this end point

    Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Overall Survival (OS)

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    End point title
    Subprotocols A, B and C (Parts 1, 2 and 3): Overall Survival (OS)
    End point description
    OS was defined as the time from the date of study Day 1 until death due to any cause. OS time (months) = (date of death - study Day 1 + 1) x 12/365.25. Any participant known to have died at the time of analysis was censored based on the last recorded date on which the participant was alive. The median was estimated using the Kaplan-Meier method and the 95% confidence interval was estimated using the method by Kalbfleisch and Prentice. 9999 = median and upper limit not calculable due to fewer than 50% events. Lower bound was calculated from observed data that was available (25% percentile). 99999 = upper limit was not calculable due to low number of events. Safety Analysis Set: Included all participants who were enrolled and received at least 1 dose of acapatamab or AMG 404 (Subprotocol C only).
    End point type
    Secondary
    End point timeframe
    From the date of study Day 1 until death due to any cause (up to a maximum of 3 years).
    End point values
    Subprotocol A: Acapatamab and Enzalutamide Subprotocol B: Acapatamab and Abiraterone Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404 Subprotocol C, Part 3: AMG 404 Monotherapy
    Number of subjects analysed
    14
    14
    15
    10
    Units: months
        median (confidence interval 95%)
    9999 (10.97 to 9999)
    21.75 (13.17 to 99999)
    16.82 (12.06 to 99999)
    9999 (0.33 to 9999)
    No statistical analyses for this end point

    Secondary: Subprotocols A, B and C: PSA Progression Free Survival (PFS)

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    End point title
    Subprotocols A, B and C: PSA Progression Free Survival (PFS)
    End point description
    PSA PFS was defined as the interval from study Day 1 to the earlier of a PSA progression or death from any cause; otherwise, PSA PFS was censored on the date of the last PSA measurement. If a participant had no baseline or post-baseline PSA measurement and a vital status of alive or known, PSA PFS was censored at study Day 1. The median was estimated using the Kaplan-Meier method and the 95% confidence interval was estimated using the method by Brookmeyer and Crowley. 99999 = upper limit was not calculable due to low number of events. Safety Analysis Set: Included all participants who were enrolled and received at least 1 dose of acapatamab or AMG 404 (Subprotocol C only).
    End point type
    Secondary
    End point timeframe
    From study Day 1 to the earlier of a PSA progression or death from any cause (up to a maximum of 3 years).
    End point values
    Subprotocol A: Acapatamab and Enzalutamide Subprotocol B: Acapatamab and Abiraterone Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404 Subprotocol C, Part 3: AMG 404 Monotherapy
    Number of subjects analysed
    14
    14
    15
    10
    Units: months
        median (confidence interval 95%)
    20.30 (3.35 to 99999)
    6.31 (3.94 to 99999)
    3.94 (2.37 to 10.64)
    4.30 (2.76 to 99999)
    No statistical analyses for this end point

    Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Clinical PFS

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    End point title
    Subprotocols A, B and C (Parts 1, 2 and 3): Clinical PFS
    End point description
    Clinical PFS was defined as the time from the first dose of acapatamab or AMG 404 (subprotocol C only) to clinical disease progression or death from any cause; otherwise, clinical PFS was censored on the date of last disease assessment. If a participant had no post-baseline disease assessment and a vital status of alive or known, clinical PFS was censored at study Day 1. The median was estimated using the Kaplan-Meier method and the 95% confidence interval was estimated using the method by Brookmeyer and Crowley. 9999 = median and upper limit not calculable due to fewer than 50% events. Lower bound was calculated from observed data that was available (25% percentile). 99999 = upper limit was not calculable due to low number of events. Safety Analysis Set: Included all participants who were enrolled and received at least 1 dose of acapatamab or AMG 404 (Subprotocol C only).
    End point type
    Secondary
    End point timeframe
    From first dose of acapatamab or AMG 404 (subprotocol C only) to clinical disease progression or death from any cause (up to a maximum of 3 years).
    End point values
    Subprotocol A: Acapatamab and Enzalutamide Subprotocol B: Acapatamab and Abiraterone Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404 Subprotocol C, Part 3: AMG 404 Monotherapy
    Number of subjects analysed
    14
    14
    15
    10
    Units: months
        median (confidence interval 95%)
    20.30 (10.97 to 99999)
    15.93 (6.31 to 99999)
    15.67 (7.20 to 99999)
    9999 (3.71 to 9999)
    No statistical analyses for this end point

    Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Time to Radiographic Progression

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    End point title
    Subprotocols A, B and C (Parts 1, 2 and 3): Time to Radiographic Progression
    End point description
    Time to radiographic progression was defined as the interval from study Day 1 to radiographic progression in the absence of subsequent anticancer therapy. Time to radiographic progression was censored at the last evaluable post-baseline tumor assessment prior to subsequent anti-cancer therapy; otherwise at study Day 1. The median was estimated using the Kaplan-Meier method and the 95% confidence interval was estimated using the method by Brookmeyer and Crowley. 9999 = median and upper limit not calculable due to fewer than 50% events. Lower bound was calculated from observed data that was available (25% percentile). 99999 = upper limit was not calculable due to low number of events. Safety Analysis Set: Included all participants who were enrolled and received at least 1 dose of acapatamab or AMG 404 (Subprotocol C only).
    End point type
    Secondary
    End point timeframe
    From study Day 1 to radiographic progression in the absence of subsequent anticancer therapy (up to a maximum of 3 years).
    End point values
    Subprotocol A: Acapatamab and Enzalutamide Subprotocol B: Acapatamab and Abiraterone Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404 Subprotocol C, Part 3: AMG 404 Monotherapy
    Number of subjects analysed
    14
    14
    15
    10
    Units: months
        median (confidence interval 95%)
    9999 (11.27 to 9999)
    8.51 (3.71 to 99999)
    9999 (2.00 to 9999)
    3.48 (1.61 to 99999)
    No statistical analyses for this end point

    Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Time to PSA Progression

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    End point title
    Subprotocols A, B and C (Parts 1, 2 and 3): Time to PSA Progression
    End point description
    Time to PSA progression was defined as the interval from study Day 1 to PSA progression, otherwise time to PSA progression was censored at the last PSA assessment. The median was estimated using the Kaplan-Meier method and the 95% confidence interval was estimated using the method by Brookmeyer and Crowley. 9999 = median and upper limit not calculable due to fewer than 50% events. Lower bound was calculated from observed data that was available (25% percentile). 99999 = upper limit was not calculable due to low number of events. Safety Analysis Set: Included all participants who were enrolled and received at least 1 dose of acapatamab or AMG 404 (Subprotocol C only).
    End point type
    Secondary
    End point timeframe
    From study Day 1 to PSA progression (up to a maximum of 3 years).
    End point values
    Subprotocol A: Acapatamab and Enzalutamide Subprotocol B: Acapatamab and Abiraterone Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404 Subprotocol C, Part 3: AMG 404 Monotherapy
    Number of subjects analysed
    14
    14
    15
    10
    Units: months
        median (confidence interval 95%)
    9999 (5.09 to 9999)
    4.83 (2.99 to 99999)
    3.94 (2.37 to 99999)
    4.30 (2.76 to 99999)
    No statistical analyses for this end point

    Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Time to Subsequent Therapy

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    End point title
    Subprotocols A, B and C (Parts 1, 2 and 3): Time to Subsequent Therapy
    End point description
    Time to subsequent therapy was defined as the interval from study Day 1 to the time a participant starts/receives the subsequent cancer therapy/subsequent therapy; otherwise, time to subsequent therapy was censored at the last known date of any of the study assessments prior to initiating the subsequent cancer therapy/subsequent therapy. The median was estimated using the Kaplan-Meier method and the 95% confidence interval was estimated using the method by Brookmeyer and Crowley. 9999 = median and upper limit not calculable due to fewer than 50% events. Lower bound was calculated from observed data that was available (25% percentile). 99999 = upper limit was not calculable due to low number of events. Safety Analysis Set: Included all participants who were enrolled and received at least 1 dose of acapatamab or AMG 404 (Subprotocol C only).
    End point type
    Secondary
    End point timeframe
    From study Day 1 to the time a participant starts/receives the subsequent cancer therapy/subsequent therapy (up to a maximum of 3 years).
    End point values
    Subprotocol A: Acapatamab and Enzalutamide Subprotocol B: Acapatamab and Abiraterone Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404 Subprotocol C, Part 3: AMG 404 Monotherapy
    Number of subjects analysed
    14
    14
    15
    10
    Units: months
        median (confidence interval 95%)
    16.39 (8.84 to 20.07)
    23.52 (5.98 to 99999)
    9999 (4.40 to 9999)
    9999 (0.89 to 9999)
    No statistical analyses for this end point

    Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Percentage of Participants Who Experienced a Gallium Prostate-specific Membrane Antigen-11 (PSMA-11) Response

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    End point title
    Subprotocols A, B and C (Parts 1, 2 and 3): Percentage of Participants Who Experienced a Gallium Prostate-specific Membrane Antigen-11 (PSMA-11) Response
    End point description
    A Gallium PSMA-11 response was defined as a ≥ 50% reduction from baseline in the maximum standardized update value (SUV) using 68Gallium (68Ga)-PSMA-11 positron emission tomography (PET)/CT. PSMA-11 response percentages were based on the number of participants with a baseline PSMA assessment (defined as the last non-missing value on or prior to the pre-dose of AMG 160/AMG 404 assessments) on Cycle 1 Day 1. The 95% confidence interval was calculated based on the Clopper-Pearson method. Safety Analysis Set: Included all participants who were enrolled and received at least 1 dose of acapatamab or AMG 404 (Subprotocol C only).
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 to 14 days post-last dose of AMG 404 (each cycle was 28 days).
    End point values
    Subprotocol A: Acapatamab and Enzalutamide Subprotocol B: Acapatamab and Abiraterone Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404 Subprotocol C, Part 3: AMG 404 Monotherapy
    Number of subjects analysed
    9
    10
    13
    9
    Units: percentage of participants
        number (confidence interval 95%)
    66.7 (29.93 to 92.51)
    20.0 (2.52 to 55.61)
    23.1 (5.04 to 53.81)
    0.0 (0.00 to 33.63)
    No statistical analyses for this end point

    Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Time to Symptomatic Skeletal Events

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    End point title
    Subprotocols A, B and C (Parts 1, 2 and 3): Time to Symptomatic Skeletal Events
    End point description
    Time to symptomatic skeletal events was defined as time from study Day 1 to the first symptomatic skeletal event, otherwise time to symptomatic skeletal event was censored at the last dose of acapatamab/AMG 404 or end of safety follow-up date, whichever was later. Symptomatic skeletal events included fracture, spinal cord compression and radiation or surgery to bone. The median was estimated using the Kaplan-Meier method and the 95% confidence interval was estimated using the method by Brookmeyer and Crowley. 9999 = median and upper limit not calculable due to fewer than 50% events. Lower bound was calculated from observed data that was available (25% percentile). 999999 = median, lower and upper limits were not calculable due to very low number of events. Safety Analysis Set: Included all participants who were enrolled and received at least 1 dose of acapatamab or AMG 404 (Subprotocol C only).
    End point type
    Secondary
    End point timeframe
    From study Day 1 to the first symptomatic skeletal event (up to a maximum of 3 years).
    End point values
    Subprotocol A: Acapatamab and Enzalutamide Subprotocol B: Acapatamab and Abiraterone Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404 Subprotocol C, Part 3: AMG 404 Monotherapy
    Number of subjects analysed
    14
    14
    15
    10
    Units: months
        median (confidence interval 95%)
    9999 (13.50 to 9999)
    999999 (999999 to 999999)
    999999 (999999 to 999999)
    999999 (999999 to 999999)
    No statistical analyses for this end point

    Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Total Alkaline Phosphatase Levels

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    End point title
    Subprotocols A, B and C (Parts 1, 2 and 3): Total Alkaline Phosphatase Levels
    End point description
    Alkaline phosphatase levels were collected centrally. Safety Analysis Set: Included all participants with data available at each time point who were enrolled and received at least 1 dose of acapatamab or AMG 404 (Subprotocol C only).
    End point type
    Secondary
    End point timeframe
    Baseline and end of treatment visit (up to 14 days post-last dose of acapatamab/AMG 404. Each cycle was 28 days, maximum duration of acapatamab treatment was 98.4 weeks/AMG 404 treatment was 105.1 weeks).
    End point values
    Subprotocol A: Acapatamab and Enzalutamide Subprotocol B: Acapatamab and Abiraterone Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404 Subprotocol C, Part 3: AMG 404 Monotherapy
    Number of subjects analysed
    14 [33]
    13 [34]
    15 [35]
    10 [36]
    Units: U/L
    arithmetic mean (standard deviation)
        Baseline
    198.21 ( 264.79 )
    305.85 ( 356.76 )
    179.00 ( 221.12 )
    167.70 ( 219.41 )
        End of Treatment Visit
    180.00 ( 198.27 )
    329.11 ( 425.58 )
    133.70 ( 106.41 )
    398.50 ( 627.04 )
    Notes
    [33] - End of treatment visit N = 12
    [34] - End of treatment visit N = 9
    [35] - End of treatment visit N = 10
    [36] - End of treatment visit N = 6
    No statistical analyses for this end point

    Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Bone Specific Alkaline Phosphatase Levels

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    End point title
    Subprotocols A, B and C (Parts 1, 2 and 3): Bone Specific Alkaline Phosphatase Levels
    End point description
    Bone specific alkaline phosphatase levels were collected centrally. Safety Analysis Set: Included all participants with data available at each time point who were enrolled and received at least 1 dose of acapatamab or AMG 404 (Subprotocol C only).
    End point type
    Secondary
    End point timeframe
    Baseline and end of treatment visit (up to 14 days post-last dose of acapatamab/AMG 404. Each cycle was 28 days, maximum duration of acapatamab treatment was 98.4 weeks/AMG 404 treatment was 105.1 weeks).
    End point values
    Subprotocol A: Acapatamab and Enzalutamide Subprotocol B: Acapatamab and Abiraterone Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404 Subprotocol C, Part 3: AMG 404 Monotherapy
    Number of subjects analysed
    13 [37]
    12 [38]
    15 [39]
    10 [40]
    Units: ug/L
    arithmetic mean (standard deviation)
        Baseline
    56.85 ( 109.65 )
    96.29 ( 129.56 )
    44.37 ( 68.69 )
    27.89 ( 30.24 )
        End of Treatment Visit
    35.31 ( 55.21 )
    103.42 ( 165.94 )
    29.44 ( 34.98 )
    145.76 ( 238.81 )
    Notes
    [37] - End of treatment visit N = 11
    [38] - End of treatment visit N = 9
    [39] - End of treatment visit N = 9
    [40] - End of treatment visit N = 5
    No statistical analyses for this end point

    Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Lactate Dehydrogenase Levels

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    End point title
    Subprotocols A, B and C (Parts 1, 2 and 3): Lactate Dehydrogenase Levels
    End point description
    Lactate dehydrogenase levels were collected centrally. Safety Analysis Set: Included all participants with data available at each time point who were enrolled and received at least 1 dose of acapatamab or AMG 404 (Subprotocol C only).
    End point type
    Secondary
    End point timeframe
    Baseline and end of treatment visit (up to 14 days post-last dose of acapatamab/AMG 404. Each cycle was 28 days, maximum duration of acapatamab treatment was 98.4 weeks/AMG 404 treatment was 105.1 weeks).
    End point values
    Subprotocol A: Acapatamab and Enzalutamide Subprotocol B: Acapatamab and Abiraterone Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404 Subprotocol C, Part 3: AMG 404 Monotherapy
    Number of subjects analysed
    13 [41]
    13 [42]
    14 [43]
    9 [44]
    Units: U/L
    arithmetic mean (standard deviation)
        Baseline
    209.54 ( 62.41 )
    268.54 ( 117.29 )
    241.50 ( 149.98 )
    267.89 ( 263.29 )
        End of Treatment Visit
    261.18 ( 134.21 )
    210.11 ( 24.15 )
    177.00 ( 40.70 )
    238.50 ( 77.06 )
    Notes
    [41] - End of treatment visit N = 11
    [42] - End of treatment visit N = 9
    [43] - End of treatment visit N = 10
    [44] - End of treatment visit N = 6
    No statistical analyses for this end point

    Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Hemoglobin Levels

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    End point title
    Subprotocols A, B and C (Parts 1, 2 and 3): Hemoglobin Levels
    End point description
    Hemoglobin levels were collected locally. 9999 = Data not available as data was only collected for safety-follow up visit 2 for subprotocol C. Safety Analysis Set: Included all participants with data available at each time point who were enrolled and received at least 1 dose of acapatamab or AMG 404 (Subprotocol C only).
    End point type
    Secondary
    End point timeframe
    Baseline, safety follow-up visit (up to 30 days post-last dose of acapatamab/AMG 404), safety follow-up 2 (subprotocol C only, up to 5 months post-dose). Each cycle = 28 days, max acapatamab duration = 98.4 weeks, max AMG 404 duration = 105.1 weeks.
    End point values
    Subprotocol A: Acapatamab and Enzalutamide Subprotocol B: Acapatamab and Abiraterone Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404 Subprotocol C, Part 3: AMG 404 Monotherapy
    Number of subjects analysed
    14 [45]
    14 [46]
    15 [47]
    10 [48]
    Units: g/L
    arithmetic mean (standard deviation)
        Baseline
    123.70 ( 18.98 )
    125.01 ( 12.45 )
    116.51 ( 11.23 )
    122.77 ( 12.96 )
        Safety Follow-up Visit
    123.15 ( 22.45 )
    115.21 ( 13.71 )
    102.34 ( 13.82 )
    121.50 ( 12.81 )
        Safety Follow-up Visit 2
    9999 ( 9999 )
    9999 ( 9999 )
    106.86 ( 21.41 )
    112.00 ( 12.12 )
    Notes
    [45] - Safety follow-up visit N = 7 Safety follow-up visit 2 N = 0
    [46] - Safety follow-up visit N = 7 Safety follow-up visit 2 N = 0
    [47] - Safety follow-up visit N = 8 Safety follow-up visit 2 N = 6
    [48] - Safety follow-up visit N = 5 Safety follow-up visit 2 N = 3
    No statistical analyses for this end point

    Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Neutrophil-to-lymphocyte Ratio

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    End point title
    Subprotocols A, B and C (Parts 1, 2 and 3): Neutrophil-to-lymphocyte Ratio
    End point description
    Data for the neutrophil-to-lymphocyte ratio were collected locally. Neutrophil-to-lymphocyte ratio was calculated by dividing the number of absolute neutrophils by the number of lymphocytes. 9999 = Data not available as data was only collected for safety-follow up visit 2 for subprotocol C. Safety Analysis Set: Included all participants with data available at each time point who were enrolled and received at least 1 dose of acapatamab or AMG 404 (Subprotocol C only).
    End point type
    Secondary
    End point timeframe
    Baseline, safety follow-up visit (up to 30 days post-last dose of acapatamab/AMG 404), safety follow-up 2 (subprotocol C only, up to 5 months post-dose). Each cycle = 28 days, max acapatamab duration = 98.4 weeks, max AMG 404 duration = 105.1 weeks.
    End point values
    Subprotocol A: Acapatamab and Enzalutamide Subprotocol B: Acapatamab and Abiraterone Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404 Subprotocol C, Part 3: AMG 404 Monotherapy
    Number of subjects analysed
    14 [49]
    14 [50]
    15 [51]
    10 [52]
    Units: ratio
    arithmetic mean (standard deviation)
        Baseline
    4.74 ( 3.03 )
    4.93 ( 4.94 )
    4.04 ( 2.90 )
    4.40 ( 2.93 )
        Safety Follow-up Visit
    2.41 ( 1.66 )
    2.44 ( 1.14 )
    2.72 ( 1.94 )
    2.69 ( 0.82 )
        Safety Follow-up Visit 2
    9999 ( 9999 )
    9999 ( 9999 )
    4.16 ( 4.10 )
    4.73 ( 2.36 )
    Notes
    [49] - Safety follow-up visit N = 6 Safety follow-up visit 2 N = 0
    [50] - Safety follow-up visit N = 7 Safety follow-up visit 2 N = 0
    [51] - Safety follow-up visit N = 8 Safety follow-up visit 2 N = 5
    [52] - Safety follow-up visit N = 5 Safety follow-up visit 2 N = 2
    No statistical analyses for this end point

    Secondary: Subprotocols A, B and C (Parts 1, 2 and 3): Urine N-telopeptide Levels

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    End point title
    Subprotocols A, B and C (Parts 1, 2 and 3): Urine N-telopeptide Levels
    End point description
    Urine N-telopeptide levels were collected centrally. Safety Analysis Set: Included all participants with data available at each time point who were enrolled and received at least 1 dose of acapatamab or AMG 404 (Subprotocol C only).
    End point type
    Secondary
    End point timeframe
    Baseline and end of treatment visit (up to 14 days post-last dose of acapatamab/AMG 404. Each cycle was 28 days, maximum duration of acapatamab treatment was 98.4 weeks/AMG 404 treatment was 105.1 weeks).
    End point values
    Subprotocol A: Acapatamab and Enzalutamide Subprotocol B: Acapatamab and Abiraterone Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404 Subprotocol C, Part 3: AMG 404 Monotherapy
    Number of subjects analysed
    11 [53]
    9 [54]
    11 [55]
    0 [56]
    Units: nmol/mmol
    arithmetic mean (standard deviation)
        Baseline
    155.99 ( 303.45 )
    88.67 ( 43.52 )
    61.06 ( 111.99 )
    ( )
        End of Treatment Visit
    109.52 ( 100.17 )
    160.10 ( 150.76 )
    60.57 ( 70.62 )
    ( )
    Notes
    [53] - End of treatment visit N = 10
    [54] - End of treatment visit N = 4
    [55] - End of treatment visit N = 7
    [56] - No data was collected for participants in subprotocol C, part 3.
    No statistical analyses for this end point

    Secondary: Subprotocol A, B and C (Parts 1 and 2): Maximum Serum Concentration (Cmax) of Acapatamab

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    End point title
    Subprotocol A, B and C (Parts 1 and 2): Maximum Serum Concentration (Cmax) of Acapatamab
    End point description
    Serum concentrations of acapatamab were determined using a validated assay. 9999 = Data was not available due to low number of participants with available samples. Pharmacokinetic (PK) Concentration Analysis Set: Included all participants who received acapatamab and had at least 1 PK concentration available for analysis.
    End point type
    Secondary
    End point timeframe
    Cycle 1: Days 1 to 7 and Cycle 2: Days 1 to 14 (each cycle was 28 days).
    End point values
    Subprotocol A (Cohort 1a): Acapatamab and Enzalutamide Subprotocol A (Cohort 1b): Acapatamab and Enzalutamide Subprotocol A (Cohort 2a): Acapatamab and Enzalutamide Subprotocol A (Cohort 2b): Acapatamab and Enzalutamide Subprotocol B (Cohort 1): Acapatamab and Abiraterone Subprotocol B (Cohort 2): Acapatamab and Abiraterone Subprotocol B (Cohort 2, Expansion): Acapatamab & Abiraterone Subprotocol C, Parts 1 & 2 (Exploration): Acapatamab & AMG 404 Subprotocol C, Parts 1 & 2 (Expansion): Acapatamab & AMG 404
    Number of subjects analysed
    3 [57]
    3 [58]
    3 [59]
    3 [60]
    4 [61]
    5 [62]
    4 [63]
    8 [64]
    4 [65]
    Units: ng/mL
    geometric mean (geometric coefficient of variation)
        Cycle 1
    10.5 ( 7 )
    7.24 ( 19 )
    8.20 ( 29 )
    7.83 ( 9999 )
    9.30 ( 33 )
    10.4 ( 55 )
    8.74 ( 23 )
    11.6 ( 49 )
    16.4 ( 35 )
        Cycle 2
    51.4 ( 9999 )
    21.4 ( 729 )
    30.7 ( 9999 )
    31.1 ( 32 )
    19.5 ( 402 )
    66.7 ( 35 )
    38.2 ( 73 )
    21.3 ( 167 )
    27.8 ( 43 )
    Notes
    [57] - Cycle 2 N = 2
    [58] - Cycle 2 N = 3
    [59] - Cycle 2 N = 2
    [60] - Cycle 1 N = 2
    [61] - Cycle 2 N = 4
    [62] - Cycle 2 N = 3
    [63] - Cycle 2 N = 4
    [64] - Cycle 2 N = 6
    [65] - Cycle 2 N = 3
    No statistical analyses for this end point

    Secondary: Subprotocol A. B and C (Parts 1 and 2): Area Under the Curve During a Dosing Interval (AUCtau)

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    End point title
    Subprotocol A. B and C (Parts 1 and 2): Area Under the Curve During a Dosing Interval (AUCtau)
    End point description
    Serum concentrations of acapatamab were determined using a validated assay. 9999 = Data was not available due to low number of participants with available samples. PK Concentration Analysis Set: Included all participants who received acapatamab and had at least 1 PK concentration available for analysis.
    End point type
    Secondary
    End point timeframe
    Cycle 1: Days 1 to 7 and Cycle 2: Days 1 to 14 (each cycle was 28 days).
    End point values
    Subprotocol A (Cohort 1a): Acapatamab and Enzalutamide Subprotocol A (Cohort 1b): Acapatamab and Enzalutamide Subprotocol A (Cohort 2a): Acapatamab and Enzalutamide Subprotocol A (Cohort 2b): Acapatamab and Enzalutamide Subprotocol B (Cohort 1): Acapatamab and Abiraterone Subprotocol B (Cohort 2): Acapatamab and Abiraterone Subprotocol B (Cohort 2, Expansion): Acapatamab & Abiraterone Subprotocol C, Parts 1 & 2 (Exploration): Acapatamab & AMG 404 Subprotocol C, Parts 1 & 2 (Expansion): Acapatamab & AMG 404
    Number of subjects analysed
    0 [66]
    2 [67]
    3 [68]
    3 [69]
    1 [70]
    2 [71]
    4 [72]
    4 [73]
    3 [74]
    Units: hr•ng/mL
    geometric mean (geometric coefficient of variation)
        Cycle 1
    ( )
    867 ( 9999 )
    906 ( 22 )
    883 ( 9999 )
    9999 ( 9999 )
    1330 ( 9999 )
    962 ( 27 )
    1270 ( 72 )
    1960 ( 19 )
        Cycle 2
    ( )
    5510 ( 9999 )
    4400 ( 9999 )
    2700 ( 39 )
    291 ( 9999 )
    4510 ( 9999 )
    2900 ( 66 )
    2490 ( 145 )
    2310 ( 69 )
    Notes
    [66] - No participants had available samples.
    [67] - Cycle 1 N = 1
    [68] - Cycle 2 N = 1
    [69] - Cycle 1 N = 2
    [70] - Cycle 1 N = 0
    [71] - Cycle 2 N = 2
    [72] - Cycle 2 N = 4
    [73] - Cycle 2 N = 4
    [74] - Cycle 2 N = 3
    No statistical analyses for this end point

    Secondary: Subprotocols A, B and C (Parts 1 and 2): Accumulation Ratio of Acapatamab

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    End point title
    Subprotocols A, B and C (Parts 1 and 2): Accumulation Ratio of Acapatamab
    End point description
    Serum concentrations of acapatamab were determined using a validated assay. Accumulation ratio was not calculated due to the differences in dosing length and dosage between the lead in dose and the target dose administrations.
    End point type
    Secondary
    End point timeframe
    Cycle 1: Days 1 to 7 and Cycle 2: Days 1 to 14 (each cycle was 28 days).
    End point values
    Subprotocol A (Cohort 1a): Acapatamab and Enzalutamide Subprotocol A (Cohort 1b): Acapatamab and Enzalutamide Subprotocol A (Cohort 2a): Acapatamab and Enzalutamide Subprotocol A (Cohort 2b): Acapatamab and Enzalutamide Subprotocol B (Cohort 1): Acapatamab and Abiraterone Subprotocol B (Cohort 2): Acapatamab and Abiraterone Subprotocol B (Cohort 2, Expansion): Acapatamab & Abiraterone Subprotocol C, Parts 1 & 2 (Exploration): Acapatamab & AMG 404
    Number of subjects analysed
    0 [75]
    0 [76]
    0 [77]
    0 [78]
    0 [79]
    0 [80]
    0 [81]
    0 [82]
    Units: ratio
        geometric mean (geometric coefficient of variation)
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    Notes
    [75] - Accumulation ratio was not calculated.
    [76] - Accumulation ratio was not calculated.
    [77] - Accumulation ratio was not calculated.
    [78] - Accumulation ratio was not calculated.
    [79] - Accumulation ratio was not calculated.
    [80] - Accumulation ratio was not calculated.
    [81] - Accumulation ratio was not calculated.
    [82] - Accumulation ratio was not calculated.
    No statistical analyses for this end point

    Secondary: Subprotocols A, B and C (Parts 1 and 2): Terminal half-life (t1/2z) of Acapatamab

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    End point title
    Subprotocols A, B and C (Parts 1 and 2): Terminal half-life (t1/2z) of Acapatamab
    End point description
    Serum concentrations of acapatamab were determined using a validated assay. 9999 = Data was not available due to low number of participants with available samples. PK Concentration Analysis Set: Included all participants who received acapatamab and had at least 1 PK concentration available for analysis.
    End point type
    Secondary
    End point timeframe
    Cycle 2: Days 1 to 14 (each cycle was 28 days).
    End point values
    Subprotocol A (Cohort 1a): Acapatamab and Enzalutamide Subprotocol A (Cohort 1b): Acapatamab and Enzalutamide Subprotocol A (Cohort 2a): Acapatamab and Enzalutamide Subprotocol A (Cohort 2b): Acapatamab and Enzalutamide Subprotocol B (Cohort 1): Acapatamab and Abiraterone Subprotocol B (Cohort 2): Acapatamab and Abiraterone Subprotocol B (Cohort 2, Expansion): Acapatamab & Abiraterone Subprotocol C, Parts 1 & 2 (Exploration): Acapatamab & AMG 404 Subprotocol C, Parts 1 & 2 (Expansion): Acapatamab & AMG 404
    Number of subjects analysed
    1
    1
    1
    3
    1
    2
    4
    3
    3
    Units: hours
        geometric mean (geometric coefficient of variation)
    64.2 ( 9999 )
    83.1 ( 9999 )
    111 ( 9999 )
    113 ( 3 )
    74.4 ( 9999 )
    107 ( 9999 )
    98.3 ( 17 )
    84.4 ( 37 )
    107 ( 25 )
    No statistical analyses for this end point

    Secondary: Subprotocol C, Part 3: Number of Participants Who Experienced a TEAE

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    End point title
    Subprotocol C, Part 3: Number of Participants Who Experienced a TEAE [83]
    End point description
    A TEAE was defined as any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment that started after the first dose of AMG 404, whichever was earlier. A treatment-related TEAE was defined as a TEAE that had a reasonable possibility of being caused by AMG 404. Clinically significant changes from baseline in vital signs and clinical laboratory tests were also recorded as TEAEs. Safety Analysis Set: Included all participants who were enrolled and received at least 1 dose of AMG 404.
    End point type
    Secondary
    End point timeframe
    From first dose of AMG 404 to the first of 30 days after last dose of AMG 404, end of study date or the initiation of a new anticancer therapy (up to a maximum of 3 years).
    Notes
    [83] - 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: No statistical analyses were pre-planned for this endpoint.
    End point values
    Subprotocol C, Part 3: AMG 404 Monotherapy
    Number of subjects analysed
    10
    Units: participants
        At least 1 TEAE
    10
        At least 1 treatment-related TEAE
    7
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Death: 1st dose of acapatamab/AMG 404 to end of study (up to a maximum of 3 years). TEAE: 1st dose of acapatamab/AMG 404 to min end of treatment + 30 days, end of study, 1st new anti-cancer therapy) (up to a maximum of 3 years)
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    26.0
    Reporting groups
    Reporting group title
    Subprotocol A: Acapatamab and Enzalutamide
    Reporting group description
    In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) eIV infusion, followed by the target dose (60-minute IV infusion) for the following doses throughout the first cycle. In subsequent cycles, participants received acapatamab at the target dose in 28-day cycles. Participants also received enzalutamide as oral tablets or oral capsules.

    Reporting group title
    Subprotocol B: Acapatamab and Abiraterone
    Reporting group description
    In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) eIV infusion, followed by the target dose (60-minute IV infusion) for the following doses throughout the first cycle. In subsequent cycles, participants received acapatamab at the target dose in 28-day cycles. Participants also received abiraterone as oral tablets and prednisone (or prednisolone in some regions).

    Reporting group title
    Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404
    Reporting group description
    In Cycle 1, participants initially received acapatamab as a 3-day (ie, 72-hour) eIV infusion, followed by the target dose (60-minute IV infusion) for the following doses throughout the first cycle. In subsequent cycles (≥ 2), participants received acapatamab at the target dose in 28-day cycles. Participants also received abiraterone as oral tablets and prednisone (or prednisolone in some regions). Participants also received AMG 404 as a short-term 30 minute IV infusion once per cycle.

    Reporting group title
    Subprotocol C, Part 3: AMG 404 Monotherapy
    Reporting group description
    Participants received AMG 404 as a short-term 30-minute IV infusion once during each cycle.

    Serious adverse events
    Subprotocol A: Acapatamab and Enzalutamide Subprotocol B: Acapatamab and Abiraterone Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404 Subprotocol C, Part 3: AMG 404 Monotherapy
    Total subjects affected by serious adverse events
         subjects affected / exposed
    10 / 14 (71.43%)
    9 / 14 (64.29%)
    11 / 15 (73.33%)
    1 / 10 (10.00%)
         number of deaths (all causes)
    4
    5
    8
    2
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Asthenia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Cytokine release syndrome
         subjects affected / exposed
    6 / 14 (42.86%)
    4 / 14 (28.57%)
    3 / 15 (20.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    14 / 14
    5 / 5
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Platelet count decreased
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural haematoma
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Product prescribing error
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    2 / 15 (13.33%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Myocardial infarction
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 14 (0.00%)
    2 / 14 (14.29%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Immune effector cell-associated neurotoxicity syndrome
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myasthenia gravis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal cord compression
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Thrombocytopenia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphopenia
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    2 / 15 (13.33%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Uveitis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Glaucoma
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Erythema multiforme
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rash
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rash maculo-papular
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Pain in extremity
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    COVID-19
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 14 (7.14%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal sepsis
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Subprotocol A: Acapatamab and Enzalutamide Subprotocol B: Acapatamab and Abiraterone Subprotocol C, Parts 1 and 2: Acapatamab and AMG 404 Subprotocol C, Part 3: AMG 404 Monotherapy
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    14 / 14 (100.00%)
    14 / 14 (100.00%)
    15 / 15 (100.00%)
    10 / 10 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour pain
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Vascular disorders
    Embolism venous
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Flushing
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Hot flush
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Hypertension
         subjects affected / exposed
    1 / 14 (7.14%)
    2 / 14 (14.29%)
    3 / 15 (20.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    3
    3
    0
    Thrombophlebitis
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Pallor
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Peripheral artery thrombosis
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Phlebitis
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Hypotension
         subjects affected / exposed
    3 / 14 (21.43%)
    1 / 14 (7.14%)
    5 / 15 (33.33%)
    0 / 10 (0.00%)
         occurrences all number
    6
    1
    7
    0
    Surgical and medical procedures
    Functional endoscopic sinus surgery
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    General disorders and administration site conditions
    Facial pain
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Chills
         subjects affected / exposed
    4 / 14 (28.57%)
    2 / 14 (14.29%)
    8 / 15 (53.33%)
    0 / 10 (0.00%)
         occurrences all number
    9
    4
    21
    0
    Chest pain
         subjects affected / exposed
    0 / 14 (0.00%)
    3 / 14 (21.43%)
    0 / 15 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    3
    0
    4
    Axillary pain
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Asthenia
         subjects affected / exposed
    5 / 14 (35.71%)
    3 / 14 (21.43%)
    2 / 15 (13.33%)
    2 / 10 (20.00%)
         occurrences all number
    13
    3
    4
    2
    Fatigue
         subjects affected / exposed
    5 / 14 (35.71%)
    5 / 14 (35.71%)
    11 / 15 (73.33%)
    3 / 10 (30.00%)
         occurrences all number
    5
    8
    20
    3
    Pyrexia
         subjects affected / exposed
    4 / 14 (28.57%)
    4 / 14 (28.57%)
    10 / 15 (66.67%)
    1 / 10 (10.00%)
         occurrences all number
    10
    4
    25
    1
    Peripheral swelling
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Oedema peripheral
         subjects affected / exposed
    2 / 14 (14.29%)
    1 / 14 (7.14%)
    2 / 15 (13.33%)
    0 / 10 (0.00%)
         occurrences all number
    3
    1
    5
    0
    Oedema
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Malaise
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Localised oedema
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Injection site reaction
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Influenza like illness
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    4 / 15 (26.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    8
    0
    Generalised oedema
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Feeling hot
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Swelling
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Temperature regulation disorder
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Immune system disorders
    Cytokine release syndrome
         subjects affected / exposed
    13 / 14 (92.86%)
    14 / 14 (100.00%)
    13 / 15 (86.67%)
    0 / 10 (0.00%)
         occurrences all number
    90
    90
    58
    0
    Reproductive system and breast disorders
    Gynaecomastia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Pelvic discomfort
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Pelvic pain
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Testicular pain
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Catarrh
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Cough
         subjects affected / exposed
    2 / 14 (14.29%)
    2 / 14 (14.29%)
    4 / 15 (26.67%)
    0 / 10 (0.00%)
         occurrences all number
    2
    8
    7
    0
    Dysphonia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Dyspnoea
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 14 (0.00%)
    3 / 15 (20.00%)
    1 / 10 (10.00%)
         occurrences all number
    2
    0
    3
    1
    Hiccups
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hypoxia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Nasal congestion
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Nasal polyps
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Pleural effusion
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Productive cough
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    1
    Pulmonary embolism
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    2 / 15 (13.33%)
    0 / 10 (0.00%)
         occurrences all number
    0
    3
    2
    0
    Rales
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Rhinitis allergic
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    2 / 15 (13.33%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    2
    1
    Tachypnoea
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Pneumonitis
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 14 (7.14%)
    2 / 14 (14.29%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    2
    0
    0
    Confusional state
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    2 / 15 (13.33%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Delirium
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Depressed mood
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Depression
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    1
    Insomnia
         subjects affected / exposed
    2 / 14 (14.29%)
    1 / 14 (7.14%)
    2 / 15 (13.33%)
    0 / 10 (0.00%)
         occurrences all number
    2
    1
    3
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 14 (7.14%)
    7 / 14 (50.00%)
    2 / 15 (13.33%)
    0 / 10 (0.00%)
         occurrences all number
    1
    15
    5
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    2 / 14 (14.29%)
    4 / 14 (28.57%)
    2 / 15 (13.33%)
    0 / 10 (0.00%)
         occurrences all number
    2
    10
    7
    0
    Blood bilirubin increased
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Blood creatinine increased
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    2
    0
    0
    Blood thyroid stimulating hormone increased
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    1
    Coagulation time prolonged
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Inflammatory marker increased
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    International normalised ratio increased
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    1
    Neutrophil count decreased
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    1 / 10 (10.00%)
         occurrences all number
    2
    0
    1
    1
    Platelet count decreased
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    1
    0
    SARS-CoV-2 antibody test positive
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    SARS-CoV-2 test positive
         subjects affected / exposed
    1 / 14 (7.14%)
    2 / 14 (14.29%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    2
    0
    0
    Transaminases increased
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 14 (7.14%)
    2 / 15 (13.33%)
    0 / 10 (0.00%)
         occurrences all number
    1
    1
    4
    0
    Weight decreased
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    3 / 15 (20.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    3
    3
    0
    Injury, poisoning and procedural complications
    Radiation associated pain
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Eye contusion
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Fall
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    2 / 10 (20.00%)
         occurrences all number
    1
    0
    0
    3
    Congenital, familial and genetic disorders
    Gilbert's syndrome
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    1
    0
    Sinus tachycardia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    4 / 15 (26.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    4
    0
    Sinus bradycardia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Cardiac failure
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Cardiac disorder
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Bradycardia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Atrial flutter
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Atrial fibrillation
         subjects affected / exposed
    0 / 14 (0.00%)
    2 / 14 (14.29%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    2
    1
    0
    Nervous system disorders
    Lethargy
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Anosmia
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    3
    0
    0
    Balance disorder
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Brain fog
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Dizziness
         subjects affected / exposed
    0 / 14 (0.00%)
    2 / 14 (14.29%)
    2 / 15 (13.33%)
    1 / 10 (10.00%)
         occurrences all number
    0
    2
    2
    1
    Dysgeusia
         subjects affected / exposed
    3 / 14 (21.43%)
    2 / 14 (14.29%)
    2 / 15 (13.33%)
    0 / 10 (0.00%)
         occurrences all number
    4
    3
    3
    0
    Headache
         subjects affected / exposed
    4 / 14 (28.57%)
    4 / 14 (28.57%)
    5 / 15 (33.33%)
    2 / 10 (20.00%)
         occurrences all number
    7
    6
    9
    3
    Immune effector cell-associated neurotoxicity syndrome
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    4 / 15 (26.67%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    5
    0
    Nervous system disorder
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Peripheral sensory neuropathy
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Presyncope
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Sciatica
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Sensory disturbance
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Syncope
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Taste disorder
         subjects affected / exposed
    3 / 14 (21.43%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    3
    0
    1
    0
    Tremor
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Paraesthesia
         subjects affected / exposed
    4 / 14 (28.57%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    4
    1
    0
    0
    Blood and lymphatic system disorders
    Microcytic anaemia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Neutropenia
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Disseminated intravascular coagulation
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Anaemia
         subjects affected / exposed
    6 / 14 (42.86%)
    1 / 14 (7.14%)
    9 / 15 (60.00%)
    0 / 10 (0.00%)
         occurrences all number
    27
    1
    20
    0
    Thrombocytopenia
         subjects affected / exposed
    2 / 14 (14.29%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    7
    1
    0
    0
    Leukocytosis
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Ear and labyrinth disorders
    Tinnitus
         subjects affected / exposed
    2 / 14 (14.29%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    2 / 10 (20.00%)
         occurrences all number
    2
    1
    0
    2
    Presbyacusis
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Ototoxicity
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hypoacusis
         subjects affected / exposed
    3 / 14 (21.43%)
    3 / 14 (21.43%)
    4 / 15 (26.67%)
    0 / 10 (0.00%)
         occurrences all number
    4
    3
    4
    0
    Deafness neurosensory
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Deafness
         subjects affected / exposed
    3 / 14 (21.43%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    4
    0
    0
    0
    Ear pain
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Eye disorders
    Choroidal neovascularisation
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Conjunctival haemorrhage
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Dry eye
         subjects affected / exposed
    3 / 14 (21.43%)
    2 / 14 (14.29%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    3
    2
    0
    0
    Exfoliation syndrome
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Chorioretinopathy
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Central serous chorioretinopathy
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Cataract nuclear
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Cataract
         subjects affected / exposed
    3 / 14 (21.43%)
    3 / 14 (21.43%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    5
    3
    3
    0
    Blepharitis
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Astigmatism
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Angle closure glaucoma
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Age-related macular degeneration
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Eye pain
         subjects affected / exposed
    1 / 14 (7.14%)
    2 / 14 (14.29%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    1
    2
    1
    0
    Vision blurred
         subjects affected / exposed
    0 / 14 (0.00%)
    2 / 14 (14.29%)
    2 / 15 (13.33%)
    0 / 10 (0.00%)
         occurrences all number
    0
    2
    2
    0
    Retinal exudates
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Retinal degeneration
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Pseudophakia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Presbyopia
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Myopia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Keratitis
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Eyelid ptosis
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Visual acuity reduced
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Visual impairment
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Vitreous detachment
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Uveitis
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 14 (7.14%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    2
    1
    1
    0
    Gastrointestinal disorders
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Abdominal distension
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Abdominal pain
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    2 / 15 (13.33%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    4
    0
    Constipation
         subjects affected / exposed
    3 / 14 (21.43%)
    3 / 14 (21.43%)
    6 / 15 (40.00%)
    1 / 10 (10.00%)
         occurrences all number
    10
    3
    7
    1
    Diarrhoea
         subjects affected / exposed
    3 / 14 (21.43%)
    8 / 14 (57.14%)
    10 / 15 (66.67%)
    2 / 10 (20.00%)
         occurrences all number
    5
    14
    23
    3
    Dry mouth
         subjects affected / exposed
    2 / 14 (14.29%)
    3 / 14 (21.43%)
    7 / 15 (46.67%)
    0 / 10 (0.00%)
         occurrences all number
    3
    4
    10
    0
    Dyspepsia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    4
    0
    1
    0
    Eructation
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Vomiting
         subjects affected / exposed
    3 / 14 (21.43%)
    5 / 14 (35.71%)
    9 / 15 (60.00%)
    0 / 10 (0.00%)
         occurrences all number
    3
    8
    18
    0
    Proctalgia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    2
    Nausea
         subjects affected / exposed
    4 / 14 (28.57%)
    3 / 14 (21.43%)
    8 / 15 (53.33%)
    2 / 10 (20.00%)
         occurrences all number
    5
    14
    15
    2
    Haemorrhoids
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Hepatobiliary disorders
    Drug-induced liver injury
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hypertransaminasaemia
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    2
    1
    0
    0
    Skin and subcutaneous tissue disorders
    Decubitus ulcer
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Dermal cyst
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Dermatitis
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Dry skin
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    1
    0
    Eczema
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    2
    1
    0
    0
    Hyperhidrosis
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Miliaria
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Night sweats
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    0
    1
    Pruritus
         subjects affected / exposed
    0 / 14 (0.00%)
    2 / 14 (14.29%)
    2 / 15 (13.33%)
    0 / 10 (0.00%)
         occurrences all number
    0
    3
    2
    0
    Rash
         subjects affected / exposed
    3 / 14 (21.43%)
    3 / 14 (21.43%)
    1 / 15 (6.67%)
    1 / 10 (10.00%)
         occurrences all number
    4
    3
    1
    1
    Rash maculo-papular
         subjects affected / exposed
    2 / 14 (14.29%)
    2 / 14 (14.29%)
    4 / 15 (26.67%)
    0 / 10 (0.00%)
         occurrences all number
    5
    3
    7
    0
    Urticaria
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Acute kidney injury
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Bladder spasm
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Calculus urethral
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Haematuria
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    1
    0
    Nephrolithiasis
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Pollakiuria
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Renal colic
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Urinary incontinence
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    4
    0
    0
    0
    Urinary retention
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    2 / 15 (13.33%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    3
    1
    Hydronephrosis
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Groin pain
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    1
    Arthralgia
         subjects affected / exposed
    3 / 14 (21.43%)
    2 / 14 (14.29%)
    0 / 15 (0.00%)
    2 / 10 (20.00%)
         occurrences all number
    3
    3
    0
    3
    Arthritis
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Back pain
         subjects affected / exposed
    2 / 14 (14.29%)
    4 / 14 (28.57%)
    5 / 15 (33.33%)
    1 / 10 (10.00%)
         occurrences all number
    3
    7
    7
    1
    Bone pain
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Flank pain
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Fracture pain
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Immune-mediated arthritis
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Muscular weakness
         subjects affected / exposed
    3 / 14 (21.43%)
    1 / 14 (7.14%)
    1 / 15 (6.67%)
    1 / 10 (10.00%)
         occurrences all number
    4
    1
    1
    2
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    1
    Myalgia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    2
    0
    Neck pain
         subjects affected / exposed
    1 / 14 (7.14%)
    2 / 14 (14.29%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    1
    2
    1
    0
    Osteonecrosis of jaw
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Pain in extremity
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    1 / 15 (6.67%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    1
    1
    Pain in jaw
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Muscle spasms
         subjects affected / exposed
    0 / 14 (0.00%)
    3 / 14 (21.43%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    3
    1
    0
    Infections and infestations
    Urinary tract infection bacterial
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Abscess
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Bacteraemia
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    COVID-19
         subjects affected / exposed
    4 / 14 (28.57%)
    1 / 14 (7.14%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    4
    1
    1
    0
    Herpes simplex reactivation
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    2 / 15 (13.33%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Urinary tract infection
         subjects affected / exposed
    3 / 14 (21.43%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    3
    1
    0
    0
    Sinusitis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Rash pustular
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Parotitis
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Oral candidiasis
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    2 / 15 (13.33%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    2
    0
    Nasopharyngitis
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Mucosal infection
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    1 / 15 (6.67%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Influenza
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Infection
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Hordeolum
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Vascular device infection
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    5 / 14 (35.71%)
    3 / 14 (21.43%)
    5 / 15 (33.33%)
    1 / 10 (10.00%)
         occurrences all number
    5
    3
    6
    1
    Hypercalcaemia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hyperglycaemia
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 14 (0.00%)
    2 / 15 (13.33%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    4
    0
    Hyperkalaemia
         subjects affected / exposed
    2 / 14 (14.29%)
    1 / 14 (7.14%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    3
    2
    0
    0
    Hyperphosphataemia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    1
    Hypoalbuminaemia
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 14 (0.00%)
    2 / 15 (13.33%)
    0 / 10 (0.00%)
         occurrences all number
    3
    0
    6
    0
    Hypocalcaemia
         subjects affected / exposed
    0 / 14 (0.00%)
    2 / 14 (14.29%)
    0 / 15 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    5
    0
    1
    Hypokalaemia
         subjects affected / exposed
    2 / 14 (14.29%)
    2 / 14 (14.29%)
    5 / 15 (33.33%)
    0 / 10 (0.00%)
         occurrences all number
    2
    2
    7
    0
    Hypomagnesaemia
         subjects affected / exposed
    0 / 14 (0.00%)
    2 / 14 (14.29%)
    2 / 15 (13.33%)
    0 / 10 (0.00%)
         occurrences all number
    0
    2
    3
    0
    Hyponatraemia
         subjects affected / exposed
    1 / 14 (7.14%)
    2 / 14 (14.29%)
    0 / 15 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    1
    2
    0
    1
    Hypophosphataemia
         subjects affected / exposed
    2 / 14 (14.29%)
    2 / 14 (14.29%)
    4 / 15 (26.67%)
    0 / 10 (0.00%)
         occurrences all number
    2
    5
    5
    0
    Malnutrition
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Dehydration
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 14 (0.00%)
    0 / 15 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    21 Oct 2020
    The following updates were made to the master protocol: - Removed Appendix 3 (Safety Events: Definitions and Procedures for Recording, Evaluating, Follow-up and Reporting) as this appendix was added to all subprotocols. - Additional changes were made to align with subprotocol amendments (removal of electrocardiograms from endpoint and “subject’s legally acceptable representative”).
    30 Mar 2021
    The following updates were made to the master protocol: - Clarified that participant randomization into subprotocols depended on upon slot availability . - Approximate total participant enrollment was updated to align with changes made in subprotocols A, B, and C (addition of Asia cohort). - Administrative changes and minor changes to align with protocol template were made.
    13 May 2021
    The following updates were made to the master protocol: - Included a new subprotocol ((Subprotocol D: A Phase 1b Study Evaluating the Safety and Efficacy of AMG 160 Monotherapy in Subjects With Metastatic Castration Resistant Prostate Cancer [mCRPC]). The study schema, number of participants and measures to minimize bias were updated. - The primary endpoint was clarified to indicate that dose-limiting toxicities are only an endpoint for the dose exploration phase of associated subprotocols. - Reference included to the master informed consent form.
    16 Jul 2021
    The following updates were made to the master protocol: - Clarified the definition of screen failures. - Aligned with updated protocol template. - Minor clarifications to language. - Administrative and editorial changes throughout protocol.
    21 Feb 2022
    The following updates were made: - Study Governance Considerations were updated to include that Amgen or its designee reserved the right to stop one or multiple subprotocols in addition to the study or study site participation. - In case tocilizumab is not available, siltuximab language was added to include instructions for administration and conduction of a subgroup analysis of safety with cytokine release syndrome outcome and pharmacokinetics for participants who received siltuximab treatment. - Since an analysis based on RECIST 1.1 without PCWG3 modifications was performed, secondary endpoint was updated to remove PCWG3 modifications for RECIST assessment. PCWG3 recommended endpoints were also, albeit separately, evaluated. - Anemia was added as a new hematology-related sign and symptom of cytokine release syndrome. - The approximate number of participants to be enrolled in subprotocols A-D was updated to 136 participants to reflect a change made in the number of participants to be enrolled for subprotocol C (reduced to 30). - A clarification was provided to specify that countries in Asia did not participate in subprotocol D. - A clarification was provided to align naming of the investigational product AMG 160 in study protocol with the name used in Investigator’s Brochure, Acapatamab. - Reference section was updated to add two citations supporting the newly added siltuximab language. - Administrative and editorial changes (including grammatical, typographical, and formatting) were made throughout 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.
    Study 20190505 (including all subprotocols) was discontinued early after a strategic decision by Amgen. This study was not stopped for safety reasons or lack of efficacy.
    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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