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    Clinical Trial Results:
    A Phase 2b, Open-label, Single-arm Study of Zanidatamab (ZW25) Monotherapy in Participants with Advanced or Metastatic HER2-amplified Biliary Tract Cancers

    Summary
    EudraCT number
    		 2020-000459-11
    Trial protocol
    		 FR   GB   IT  
    Global end of trial date
    11 Jul 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    27 Jul 2025
    First version publication date
    27 Jul 2025
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    ZWI-ZW25-203
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04466891
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Jazz Pharmaceuticals, Inc.
    Sponsor organisation address
    3170 Porter Drive, Palo Alto, United States, 94304
    Public contact
    Director Clinical Trial Disclosure & Transparency, Jazz Pharmaceuticals, Inc., +1 2158323750, ClinicalTrialDisclosure@JazzPharma.com
    Scientific contact
    Director Clinical Trial Disclosure & Transparency, Jazz Pharmaceuticals, Inc., +1 2158323750, ClinicalTrialDisclosure@JazzPharma.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
    11 Jul 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    11 Jul 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of the trial was to evaluate the anti-tumor activity of zanidatamab monotherapy in participants with advanced or metastatic HER2-amplified biliary tract cancers (BTC) by evaluating the confirmed ORR by RECIST v1.1, assessed by Independent Central Review.
    Protection of trial subjects
    This trial was conducted in compliance with the protocol, ICH GCP guidelines, the ethical principles of the Declaration of Helsinki, and applicable local laws and regulatory requirements.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    15 Sep 2020
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    China: 24
    Country: Number of subjects enrolled
    Korea, Republic of: 31
    Country: Number of subjects enrolled
    Canada: 1
    Country: Number of subjects enrolled
    United States: 17
    Country: Number of subjects enrolled
    Chile: 1
    Country: Number of subjects enrolled
    France: 4
    Country: Number of subjects enrolled
    United Kingdom: 2
    Country: Number of subjects enrolled
    Italy: 3
    Country: Number of subjects enrolled
    Spain: 4
    Worldwide total number of subjects
    87
    EEA total number of subjects
    11
    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)
    45
    From 65 to 84 years
    42
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 A total of 87 participants who met all eligibility criteria were enrolled and received treatment.

    Pre-assignment
    Screening details
    		 Participants must have received at least 1 prior gemcitabine-containing systemic chemotherapy regimen for advanced disease and experienced disease progression after or developed intolerance to the most recent prior therapy.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Cohort I
    Arm description
    		 Participants with advanced or metastatic biliary tract cancer with HER2 amplification by in situ hybridization (ISH) and HER2 overexpression by immunohistochemistry (IHC) which includes IHC 2+ or 3+
    Arm type
    		 Experimental

    Investigational medicinal product name
    Zanidatamab
    Investigational medicinal product code
    Other name
    ZIIHERA®, ZW25, JZP598
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered at 20 mg/kg on Days 1 and 15 of each 28-day cycle

    Arm title
    		 Cohort II
    Arm description
    		 Participants with advanced or metastatic biliary tract cancer with HER2 amplification by ISH and HER2 IHC 0 or 1+.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Zanidatamab
    Investigational medicinal product code
    Other name
    ZIIHERA®, ZW25, JZP598
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered at 20 mg/kg on Days 1 and 15 of each 28-day cycle

    Number of subjects in period 1
    		Cohort I Cohort II
    Started
    80
    7
    Completed
    0
    0
    Not completed
    80
    7
         Adverse event, serious fatal
    60
    6
         Transitioned to Named Patient Supply (NPS) program
    5
    -
         Study terminated by sponsor
    5
    -
         Withdrawal of consent
    8
    1
         Lost to follow-up
    2
    -

    Baseline characteristics

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    Subject analysis sets

    Subject analysis set title
    Cohort I
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Participants with advanced or metastatic biliary tract cancer with HER2 amplification by in situ hybridization (ISH) and HER2 overexpression by immunohistochemistry (IHC) which includes IHC 2+ or 3+

    Subject analysis set title
    Cohort II
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Participants with advanced or metastatic biliary tract cancer with HER2 amplification by ISH and HER2 IHC 0 or 1+.

    Subject analysis sets values
    		 Cohort I Cohort II
    Number of subjects
    80
    7
    Age categorical
    Units: Subjects
        In Utero
    0
    0
        Preterm newborn infants (gestional age < 37 wks)
    0
    0
        Newborns (0-27 days)
    0
    0
        Infants and toddlers (28 days - 23 months)
    0
    0
        Children (2 - 11 years)
    0
    0
        12 - 17 years
    0
    0
        Adults (18 - 64 years)
    41
    4
        From 65 - 84 years
    39
    3
        85 years and over
    0
    0
    Age continuous
    Units:
        
    ( )
    ( )
    Gender categorical
    Units: Subjects
        Male
    35
    5
        Female
    45
    2

    End points

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    End points reporting groups
    Reporting group title
    Cohort I
    Reporting group description
    		 Participants with advanced or metastatic biliary tract cancer with HER2 amplification by in situ hybridization (ISH) and HER2 overexpression by immunohistochemistry (IHC) which includes IHC 2+ or 3+

    Reporting group title
    Cohort II
    Reporting group description
    		 Participants with advanced or metastatic biliary tract cancer with HER2 amplification by ISH and HER2 IHC 0 or 1+.

    Subject analysis set title
    Cohort I
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Participants with advanced or metastatic biliary tract cancer with HER2 amplification by in situ hybridization (ISH) and HER2 overexpression by immunohistochemistry (IHC) which includes IHC 2+ or 3+

    Subject analysis set title
    Cohort II
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Participants with advanced or metastatic biliary tract cancer with HER2 amplification by ISH and HER2 IHC 0 or 1+.

    Primary: Confirmed Objective Response Rate (ORR) by Independent Central Review (ICR)

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    End point title
    		 Confirmed Objective Response Rate (ORR) by Independent Central Review (ICR) [1]
    End point description
    Number of participants who achieved a confirmed best overall response (BOR) of either complete response (CR) or partial response (PR) during treatment per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete response (CR) is defined as a disappearance of all target and non-target lesions and partial response (PR) is defined as at least a 30% decrease in the sum of diameters of all target lesions.
    End point type
    Primary
    End point timeframe
    Up to 46 months
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: This outcome measure was assessed using descriptive statistics.
    End point values
    		 Cohort I Cohort II
    Number of subjects analysed
    80
    7
    Units: Participants
        number (not applicable)
    33
    0
    No statistical analyses for this end point

    Secondary: Duration of Response (DOR) by ICR

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    End point title
    		 Duration of Response (DOR) by ICR
    End point description
    The time from the first confirmed objective response (CR or PR) to documented progressive disease (PD) per RECIST 1.1 or death from any cause.
    End point type
    Secondary
    End point timeframe
    Up to 46 months
    End point values
    		 Cohort I Cohort II
    Number of subjects analysed
    33
    0 [2]
    Units: months
        median (confidence interval 95%)
    14.92 (7.39 to 23.98)
    ( to )
    Notes
    [2] - Participant data were not available for assessment in this cohort.
    No statistical analyses for this end point

    Secondary: DOR ≥ 16 weeks by ICR

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    End point title
    		 DOR ≥ 16 weeks by ICR
    End point description
    Proportion of subjects with a DOR ≥ 16 weeks per RECIST 1.1
    End point type
    Secondary
    End point timeframe
    24 weeks, up to 46 months
    End point values
    		 Cohort I Cohort II
    Number of subjects analysed
    33
    0 [3]
    Units: participants
        number (not applicable)
    28
    Notes
    [3] - Participant data were not available for assessment in this cohort.
    No statistical analyses for this end point

    Secondary: Disease control rate (DCR) by ICR

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    End point title
    		 Disease control rate (DCR) by ICR
    End point description
    Number of subjects who achieved a best overall response of stable disease (SD), non-CR/non-PD, or confirmed CR or PR per RECIST 1.1
    End point type
    Secondary
    End point timeframe
    Up to 46 months
    End point values
    		 Cohort I Cohort II
    Number of subjects analysed
    80
    7
    Units: participants
        number (not applicable)
    55
    3
    No statistical analyses for this end point

    Secondary: Progression-free survival (PFS) by ICR

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    End point title
    		 Progression-free survival (PFS) by ICR
    End point description
    The time from the first dose of study treatment to the date of documented disease progression (per RECIST 1.1) or death from any cause.
    End point type
    Secondary
    End point timeframe
    Up to 46 months
    End point values
    		 Cohort I Cohort II
    Number of subjects analysed
    80
    7
    Units: months
        median (confidence interval 95%)
    5.49 (3.65 to 7.29)
    1.87 (1.22 to 1.87)
    No statistical analyses for this end point

    Secondary: ORR by Investigator Assessment

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    End point title
    		 ORR by Investigator Assessment
    End point description
    Number of subjects who achieved a confirmed BOR of either CR or PR during treatment per RECIST 1.1
    End point type
    Secondary
    End point timeframe
    Up to 46 months
    End point values
    		 Cohort I Cohort II
    Number of subjects analysed
    80
    7
    Units: participants
        number (not applicable)
    34
    0
    No statistical analyses for this end point

    Secondary: DOR by Investigator Assessment

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    End point title
    		 DOR by Investigator Assessment
    End point description
    The time from the first confirmed objective response (CR or PR) to documented PD per RECIST 1.1 or death from any cause.
    End point type
    Secondary
    End point timeframe
    Up to 46 months
    End point values
    		 Cohort I Cohort II
    Number of subjects analysed
    34
    0 [4]
    Units: months
        median (confidence interval 95%)
    11.10 (7.46 to 14.06)
    ( to )
    Notes
    [4] - Participant data were not available for assessment in this cohort.
    No statistical analyses for this end point

    Secondary: DOR ≥ 16 Weeks by Investigator Assessment

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    End point title
    		 DOR ≥ 16 Weeks by Investigator Assessment
    End point description
    Proportion of subjects with a DOR ≥ 16 weeks per RECIST 1.1
    End point type
    Secondary
    End point timeframe
    24 weeks, up to 46 months
    End point values
    		 Cohort I Cohort II
    Number of subjects analysed
    34
    0 [5]
    Units: participants
        number (not applicable)
    31
    Notes
    [5] - Participant data were not available for assessment in this cohort.
    No statistical analyses for this end point

    Secondary: DCR by Investigator Assessment

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    End point title
    		 DCR by Investigator Assessment
    End point description
    Number of subjects who achieved a best overall response of stable disease (SD), non-CR/non-PD, or confirmed CR or PR per RECIST 1.1
    End point type
    Secondary
    End point timeframe
    Up to 46 months
    End point values
    		 Cohort I Cohort II
    Number of subjects analysed
    80
    7
    Units: participants
        number (not applicable)
    54
    1
    No statistical analyses for this end point

    Secondary: PFS by Investigator Assessment

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    End point title
    		 PFS by Investigator Assessment
    End point description
    The time from the first dose of study treatment to the date of documented disease progression (per RECIST 1.1) or death from any cause.
    End point type
    Secondary
    End point timeframe
    Up to 46 months
    End point values
    		 Cohort I Cohort II
    Number of subjects analysed
    80
    7
    Units: months
        median (confidence interval 95%)
    5.37 (3.55 to 7.29)
    1.77 (0.79 to 1.94)
    No statistical analyses for this end point

    Secondary: Overall Survival

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    End point title
    		 Overall Survival
    End point description
    The time from the first dose of study treatment until the date of death from any cause
    End point type
    Secondary
    End point timeframe
    Up to 46 months
    End point values
    		 Cohort I Cohort II
    Number of subjects analysed
    80
    7
    Units: months
        median (confidence interval 95%)
    15.54 (10.38 to 18.66)
    5.52 (1.22 to 5.52)
    No statistical analyses for this end point

    Secondary: Incidence of Adverse Events (AEs)

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    End point title
    		 Incidence of Adverse Events (AEs)
    End point description
    Number of subjects who experienced AEs or serious adverse events
    End point type
    Secondary
    End point timeframe
    Up to 46 months
    End point values
    		 Cohort I Cohort II
    Number of subjects analysed
    80
    7
    Units: participants
    number (not applicable)
        Any Treatment Emergent Adverse Events (TEAEs)
    78
    6
        Zanidatamab related TEAE
    61
    2
        Any Treatment Emergent Serious Adverse Event (SAE)
    43
    3
        Zanidatamab related serious TEAE
    8
    0
        Zanidatamab related TEAE led to discontinuation
    2
    0
    No statistical analyses for this end point

    Secondary: Incidence of Laboratory Abnormalities

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    End point title
    		 Incidence of Laboratory Abnormalities
    End point description
    Number of subjects who experienced a maximum severity of Grade 3 or higher post-baseline laboratory abnormality, including either hematology or chemistry. Grades are defined using National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), version 5.0
    End point type
    Secondary
    End point timeframe
    Up to 46 months
    End point values
    		 Cohort I Cohort II
    Number of subjects analysed
    80
    7
    Units: participants
        number (not applicable)
    37
    7
    No statistical analyses for this end point

    Secondary: Maximum Serum Concentration of ZW25

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    End point title
    		 Maximum Serum Concentration of ZW25
    End point description
    End point type
    Secondary
    End point timeframe
    Pre-dose, end of infusion, 2, 4, 8, 24 and 96 hours post dose
    End point values
    		 Cohort I Cohort II
    Number of subjects analysed
    16
    3
    Units: microgram per milliliter
        geometric mean (geometric coefficient of variation)
    457.6 ( 15.44 )
    443.6 ( 24.10 )
    No statistical analyses for this end point

    Secondary: Trough concentration of ZW25

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    End point title
    		 Trough concentration of ZW25
    End point description
    Minimum observed serum concentration (trough)
    End point type
    Secondary
    End point timeframe
    Pre-dose, end of infusion, 2, 4, 8, 24 and 96 hours post dose
    End point values
    		 Cohort I Cohort II
    Number of subjects analysed
    16
    3
    Units: microgram per milliliter
        geometric mean (geometric coefficient of variation)
    73.4 ( 42.10 )
    46.5 ( 18.66 )
    No statistical analyses for this end point

    Secondary: Incidence of Anti-drug Antibodies (ADAs)

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    End point title
    		 Incidence of Anti-drug Antibodies (ADAs)
    End point description
    Number of subjects who develop ADAs
    End point type
    Secondary
    End point timeframe
    Up to 46 months
    End point values
    		 Cohort I Cohort II
    Number of subjects analysed
    78
    7
    Units: participants
        number (not applicable)
    1
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were collected from the start of dosing of any study drug up until 30 days after last study dose, up to approximately 3 years 10 months (46 months).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25
    Reporting groups
    Reporting group title
    Cohort I
    Reporting group description
    		 Participants with advanced or metastatic biliary tract cancer with HER2 amplification by in situ hybridization (ISH) and HER2 overexpression by immunohistochemistry (IHC) which includes IHC 2+ or 3+

    Reporting group title
    Cohort II
    Reporting group description
    		 Participants with advanced or metastatic biliary tract cancer with HER2 amplification by ISH and HER2 IHC 0 or 1+.

    Serious adverse events
    		 Cohort I Cohort II
    Total subjects affected by serious adverse events
         subjects affected / exposed
    43 / 80 (53.75%)
    3 / 7 (42.86%)
         number of deaths (all causes)
    60
    6
         number of deaths resulting from adverse events
    2
    2
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cholangiocarcinoma
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Haemangioma
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paraneoplastic syndrome
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Aortic aneurysm
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    2 / 80 (2.50%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    0 / 80 (0.00%)
    1 / 7 (14.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pyrexia
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion
         subjects affected / exposed
    1 / 80 (1.25%)
    1 / 7 (14.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alanine aminotransferase increased
         subjects affected / exposed
    2 / 80 (2.50%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bilirubin conjugated increased
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ejection fraction decreased
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Infusion related reaction
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Abdominal lymphadenopathy
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Obstruction gastric
         subjects affected / exposed
    3 / 80 (3.75%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    2 / 80 (2.50%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    1 / 80 (1.25%)
    1 / 7 (14.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Duodenal obstruction
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspepsia
         subjects affected / exposed
    0 / 80 (0.00%)
    1 / 7 (14.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal stenosis
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Faeces discoloured
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestinal obstruction
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholangitis
         subjects affected / exposed
    3 / 80 (3.75%)
    2 / 7 (28.57%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Biliary obstruction
         subjects affected / exposed
    4 / 80 (5.00%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Jaundice
         subjects affected / exposed
    2 / 80 (2.50%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Jaundice cholestatic
         subjects affected / exposed
    5 / 80 (6.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bile duct stenosis
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic failure
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Hepatitis cholestatic
         subjects affected / exposed
    0 / 80 (0.00%)
    1 / 7 (14.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematochezia
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    4 / 80 (5.00%)
    1 / 7 (14.29%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    4 / 80 (5.00%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Biliary tract infection
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Biliary sepsis
         subjects affected / exposed
    0 / 80 (0.00%)
    1 / 7 (14.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    2 / 80 (2.50%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholangitis infective
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oral candidiasis
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver abscess
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    0 / 80 (0.00%)
    1 / 7 (14.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pseudomembranous colitis
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Malnutrition
         subjects affected / exposed
    1 / 80 (1.25%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Cohort I Cohort II
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    78 / 80 (97.50%)
    5 / 7 (71.43%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    10 / 80 (12.50%)
    0 / 7 (0.00%)
         occurrences all number
    16
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    6 / 80 (7.50%)
    1 / 7 (14.29%)
         occurrences all number
    7
    1
    Fatigue
         subjects affected / exposed
    11 / 80 (13.75%)
    0 / 7 (0.00%)
         occurrences all number
    15
    0
    Odema peripheral
         subjects affected / exposed
    5 / 80 (6.25%)
    0 / 7 (0.00%)
         occurrences all number
    5
    0
    Pyrexia
         subjects affected / exposed
    14 / 80 (17.50%)
    0 / 7 (0.00%)
         occurrences all number
    23
    0
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    3 / 80 (3.75%)
    1 / 7 (14.29%)
         occurrences all number
    3
    1
    Reproductive system and breast disorders
    Pelvic pain
         subjects affected / exposed
    0 / 80 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    0
    2
    Respiratory, thoracic and mediastinal disorders
    Epistaxis
         subjects affected / exposed
    2 / 80 (2.50%)
    1 / 7 (14.29%)
         occurrences all number
    2
    2
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    6 / 80 (7.50%)
    0 / 7 (0.00%)
         occurrences all number
    6
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    16 / 80 (20.00%)
    1 / 7 (14.29%)
         occurrences all number
    28
    1
    Aspartate aminotransferase increased
         subjects affected / exposed
    15 / 80 (18.75%)
    1 / 7 (14.29%)
         occurrences all number
    30
    1
    Blood bilirubin increased
         subjects affected / exposed
    10 / 80 (12.50%)
    0 / 7 (0.00%)
         occurrences all number
    12
    0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    7 / 80 (8.75%)
    2 / 7 (28.57%)
         occurrences all number
    10
    2
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    6 / 80 (7.50%)
    1 / 7 (14.29%)
         occurrences all number
    8
    1
    Ejection fraction decreased
         subjects affected / exposed
    11 / 80 (13.75%)
    0 / 7 (0.00%)
         occurrences all number
    12
    0
    Blood creatinine increased
         subjects affected / exposed
    6 / 80 (7.50%)
    1 / 7 (14.29%)
         occurrences all number
    10
    1
    Neutrophil count increased
         subjects affected / exposed
    0 / 80 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    0
    1
    Platelet count decreased
         subjects affected / exposed
    3 / 80 (3.75%)
    1 / 7 (14.29%)
         occurrences all number
    3
    1
    Weight decreased
         subjects affected / exposed
    11 / 80 (13.75%)
    1 / 7 (14.29%)
         occurrences all number
    13
    1
    Injury, poisoning and procedural complications
    Procedural pain
         subjects affected / exposed
    1 / 80 (1.25%)
    1 / 7 (14.29%)
         occurrences all number
    1
    1
    Infusion related reaction
         subjects affected / exposed
    27 / 80 (33.75%)
    1 / 7 (14.29%)
         occurrences all number
    30
    1
    Fall
         subjects affected / exposed
    0 / 80 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    0
    1
    Cardiac disorders
    Palpitations
         subjects affected / exposed
    0 / 80 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    0
    1
    Nervous system disorders
    Peripheral sensory neuropathy
         subjects affected / exposed
    6 / 80 (7.50%)
    0 / 7 (0.00%)
         occurrences all number
    6
    0
    Dizziness
         subjects affected / exposed
    7 / 80 (8.75%)
    0 / 7 (0.00%)
         occurrences all number
    8
    0
    Blood and lymphatic system disorders
    Anemia
         subjects affected / exposed
    18 / 80 (22.50%)
    3 / 7 (42.86%)
         occurrences all number
    25
    4
    Leukocytosis
         subjects affected / exposed
    0 / 80 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    16 / 80 (20.00%)
    0 / 7 (0.00%)
         occurrences all number
    21
    0
    Abdominal pain upper
         subjects affected / exposed
    7 / 80 (8.75%)
    0 / 7 (0.00%)
         occurrences all number
    8
    0
    Duodenal ulcer
         subjects affected / exposed
    1 / 80 (1.25%)
    1 / 7 (14.29%)
         occurrences all number
    1
    1
    Diarrhoea
         subjects affected / exposed
    39 / 80 (48.75%)
    0 / 7 (0.00%)
         occurrences all number
    106
    0
    Constipation
         subjects affected / exposed
    5 / 80 (6.25%)
    0 / 7 (0.00%)
         occurrences all number
    5
    0
    Ascites
         subjects affected / exposed
    4 / 80 (5.00%)
    1 / 7 (14.29%)
         occurrences all number
    4
    1
    Dyspepsia
         subjects affected / exposed
    5 / 80 (6.25%)
    0 / 7 (0.00%)
         occurrences all number
    6
    0
    Vomiting
         subjects affected / exposed
    13 / 80 (16.25%)
    1 / 7 (14.29%)
         occurrences all number
    20
    1
    Nausea
         subjects affected / exposed
    14 / 80 (17.50%)
    0 / 7 (0.00%)
         occurrences all number
    20
    0
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    11 / 80 (13.75%)
    0 / 7 (0.00%)
         occurrences all number
    13
    0
    Rash
         subjects affected / exposed
    7 / 80 (8.75%)
    0 / 7 (0.00%)
         occurrences all number
    7
    0
    Renal and urinary disorders
    Pollakiuria
         subjects affected / exposed
    1 / 80 (1.25%)
    1 / 7 (14.29%)
         occurrences all number
    1
    1
    Renal failure
         subjects affected / exposed
    0 / 80 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    0
    1
    Infections and infestations
    Conjunctivitis
         subjects affected / exposed
    0 / 80 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    0
    1
    COVID-19
         subjects affected / exposed
    5 / 80 (6.25%)
    1 / 7 (14.29%)
         occurrences all number
    5
    1
    Urinary tract infection
         subjects affected / exposed
    6 / 80 (7.50%)
    0 / 7 (0.00%)
         occurrences all number
    8
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    13 / 80 (16.25%)
    0 / 7 (0.00%)
         occurrences all number
    14
    0
    Hypoalbuminaemia
         subjects affected / exposed
    6 / 80 (7.50%)
    0 / 7 (0.00%)
         occurrences all number
    11
    0
    Hypomagnesaemia
         subjects affected / exposed
    5 / 80 (6.25%)
    0 / 7 (0.00%)
         occurrences all number
    8
    0
    Hypokalaemia
         subjects affected / exposed
    11 / 80 (13.75%)
    0 / 7 (0.00%)
         occurrences all number
    15
    0
    Hypochloraemia
         subjects affected / exposed
    1 / 80 (1.25%)
    1 / 7 (14.29%)
         occurrences all number
    1
    1
    Hyponatraemia
         subjects affected / exposed
    3 / 80 (3.75%)
    1 / 7 (14.29%)
         occurrences all number
    3
    1
    Hypoproteinaemia
         subjects affected / exposed
    1 / 80 (1.25%)
    1 / 7 (14.29%)
         occurrences all number
    1
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    26 Apr 2020
    Updated pain assessment questionnaires, removed quality of life questionnaires, and clarified administration procedures
    21 Apr 2021
    Clarified and revised eligibility criteria, added clarification on assessments and procedures, and updated safety reporting procedures.
    08 Sep 2023
    Administrative changes were incorporated.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

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