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    Clinical Trial Results:
    A MULTI-CENTER, OPEN-LABEL, PHASE 2 STUDY TO EVALUATE SAFETY AND EFFICACY OF U3-1402 IN SUBJECTS WITH ADVANCED OR METASTATIC COLORECTAL CANCER (CRC)

    Summary
    EudraCT number
    2019-004418-32
    Trial protocol
    GB   PL   BE   IT  
    Global end of trial date
    03 Feb 2022

    Results information
    Results version number
    v1(current)
    This version publication date
    20 Feb 2023
    First version publication date
    20 Feb 2023
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    U31402-A-U202
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT04479436
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Daiichi Sankyo, Inc.
    Sponsor organisation address
    211 Mt. Airy Rd., Basking Ridge, United States, 07920
    Public contact
    Global Clinical Director, Daiichi Sankyo, Inc., +1 908-992- 6400, CTRinfo@dsi.com
    Scientific contact
    Global Clinical Director, Daiichi Sankyo, Inc., +1 908-992- 6400, CTRinfo@dsi.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    03 Feb 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    03 Feb 2022
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To assess the tolerability and antitumor activity of U3-1402 in subjects with advanced or metastatic CRC who are resistant, refractory, or intolerant to at least 2 prior lines of therapy
    Protection of trial subjects
    The study protocol, amendments, the informed consent form(s) (ICF[s]), and information sheets were approved by the appropriate and applicable Independent Ethics Committees (IECs) or Institutional Review Boards (IRBs). The study was conducted in compliance with the protocol, the ethical principles that have their origin in the Declaration of Helsinki, the International Council for Harmonisation (ICH) consolidated Guideline E6 for Good Clinical Practice (GCP) (CPMP/ICH/135/95), and applicable regulatory requirement(s).
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    14 Aug 2020
    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: 30
    Country: Number of subjects enrolled
    Japan: 10
    Worldwide total number of subjects
    40
    EEA total number of subjects
    0
    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)
    30
    From 65 to 84 years
    10
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    A total of 40 participants were enrolled and treated at 12 sites in the United States and Japan.

    Pre-assignment
    Screening details
    60 participants were screened and 20 participants were screen failures. A total of 39 participants with high HER3 expression CRC were enrolled in Cohort 1 and 1 participant with low HER3 expression CRC was enrolled in Cohort 2.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Cohort 1: HER3 High (IHC 3+, 2+)
    Arm description
    Participants with high tumor expression levels of human epidermal receptor 3 (HER3) in a pre-treatment biopsy specimen who received 5.6 mg/Kg of U3-1402 intravenously (IV) on Day 1 of each 21-day cycle.
    Arm type
    Experimental

    Investigational medicinal product name
    U3-1402
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    U3-1402 will be dosed at 5.6 mg/kg as an intravenous (IV) infusion administered on Day 1 of each 21-day cycle.

    Arm title
    Cohort 2: HER3 Low/Negative (IHC 1+, 0)
    Arm description
    Participants with low or negative tumor expression levels of human epidermal receptor 3 (HER3) in a pre-treatment biopsy specimen who received 5.6 mg/Kg of U3-1402 intravenously (IV) on Day 1 of each 21-day cycle.
    Arm type
    Experimental

    Investigational medicinal product name
    U3-1402
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    U3-1402 will be dosed at 5.6 mg/kg as an intravenous (IV) infusion administered on Day 1 of each 21-day cycle.

    Number of subjects in period 1
    Cohort 1: HER3 High (IHC 3+, 2+) Cohort 2: HER3 Low/Negative (IHC 1+, 0)
    Started
    39
    1
    Completed
    0
    0
    Not completed
    39
    1
         Clinical progression
    1
    -
         Physician decision
    1
    -
         Adverse event, non-fatal
    6
    -
         Progressive disease
    26
    1
         Withdrawal by subject
    5
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Cohort 1: HER3 High (IHC 3+, 2+)
    Reporting group description
    Participants with high tumor expression levels of human epidermal receptor 3 (HER3) in a pre-treatment biopsy specimen who received 5.6 mg/Kg of U3-1402 intravenously (IV) on Day 1 of each 21-day cycle.

    Reporting group title
    Cohort 2: HER3 Low/Negative (IHC 1+, 0)
    Reporting group description
    Participants with low or negative tumor expression levels of human epidermal receptor 3 (HER3) in a pre-treatment biopsy specimen who received 5.6 mg/Kg of U3-1402 intravenously (IV) on Day 1 of each 21-day cycle.

    Reporting group values
    Cohort 1: HER3 High (IHC 3+, 2+) Cohort 2: HER3 Low/Negative (IHC 1+, 0) Total
    Number of subjects
    39 1 40
    Age categorical
    Units: Subjects
        In utero
    0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0
        Newborns (0-27 days)
    0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0
        Children (2-11 years)
    0 0 0
        Adolescents (12-17 years)
    0 0 0
        Adults (18-64 years)
    30 0 30
        From 65-84 years
    9 1 10
        85 years and over
    0 0 0
    Age continuous
    Units: years
        median (full range (min-max))
    56 (40 to 74) 67 (67 to 67) -
    Gender categorical
    Units: Subjects
        Female
    13 1 14
        Male
    26 0 26
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    0 0 0
        Asian
    10 0 10
        Native Hawaiian or Other Pacific Islander
    3 0 3
        Black or African American
    0 0 0
        White
    26 1 27
        More than one race
    0 0 0
        Unknown or Not Reported
    0 0 0

    End points

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    End points reporting groups
    Reporting group title
    Cohort 1: HER3 High (IHC 3+, 2+)
    Reporting group description
    Participants with high tumor expression levels of human epidermal receptor 3 (HER3) in a pre-treatment biopsy specimen who received 5.6 mg/Kg of U3-1402 intravenously (IV) on Day 1 of each 21-day cycle.

    Reporting group title
    Cohort 2: HER3 Low/Negative (IHC 1+, 0)
    Reporting group description
    Participants with low or negative tumor expression levels of human epidermal receptor 3 (HER3) in a pre-treatment biopsy specimen who received 5.6 mg/Kg of U3-1402 intravenously (IV) on Day 1 of each 21-day cycle.

    Subject analysis set title
    Cohort 1 & 2: HER3 High (IHC 3+, 2+) & HER3 Low/Negative (IHC)
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Participants with high tumor expression & low or negative levels of human epidermal receptor 3 (HER3) low or negative and who received 5.6 mg/Kg of U3-1402 intravenously (IV) on Day 1 of each 21-day cycle (Safety Analysis Set).

    Primary: Objective Response Rate (ORR) Based on Blinded Independent Central Review (BICR) Following Administration of U3-1402 in Participants with Advanced or Metastatic Colorectal Cancer

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    End point title
    Objective Response Rate (ORR) Based on Blinded Independent Central Review (BICR) Following Administration of U3-1402 in Participants with Advanced or Metastatic Colorectal Cancer [1] [2]
    End point description
    The Objective Response Rate (ORR) was defined as the percentage of participants who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), assessed by blinded independent central review (BICR) based on RECIST version 1.1. CR was defined as a reduction of target lesions to non-measurable dimensions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. Confirmed ORR based on BICR is reported and was assessed in the Full Analysis Set.
    End point type
    Primary
    End point timeframe
    From baseline up to disease progression by BICR, death, lost to follow up, or withdrawal of consent by subject (whichever occurs first), up to approximately 16.9 months
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No further statistical analysis performed as this is a single arm study with no comparators.
    [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: Only 1 participant was enrolled into cohort 2, data for this one participant was presented descriptively and was not summarized in aggregated form.
    End point values
    Cohort 1: HER3 High (IHC 3+, 2+)
    Number of subjects analysed
    39
    Units: Percentage of Participants
        number (confidence interval 95%)
    5.1 (0.6 to 17.3)
    No statistical analyses for this end point

    Secondary: Duration of Response (DOR) Based on Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 in Participants with Advanced or Metastatic Colorectal Cancer

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    End point title
    Duration of Response (DOR) Based on Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 in Participants with Advanced or Metastatic Colorectal Cancer [3]
    End point description
    Duration of Response (DOR) was defined as the time from the date of the first documentation of objective response (complete response [CR] or partial response [PR]) to the date of the first objective documentation of progressive disease (PD) or death due to any cause. DOR based on BICR and Investigator assessment and was calculated for responders (participants with CR/PR) only.
    End point type
    Secondary
    End point timeframe
    From baseline up to disease progression by BICR, death, lost to follow up, or withdrawal of consent by subject (whichever occurs first), up to approximately 16.9 months
    Notes
    [3] - 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: Only 1 participant was enrolled into cohort 2, data for this one participant was presented descriptively and was not summarized in aggregated form.
    End point values
    Cohort 1: HER3 High (IHC 3+, 2+)
    Number of subjects analysed
    2
    Units: months
    median (confidence interval 95%)
        Duration of Response based on BICR
    2.91 (2.79 to 3.02)
        Duration of Response based on Investigator
    4.48 (2.56 to 6.41)
    No statistical analyses for this end point

    Secondary: Objective Response Rate (ORR) Based on Investigator Following Administration of U3-1402 in Participants with Advanced or Metastatic Colorectal Cancer

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    End point title
    Objective Response Rate (ORR) Based on Investigator Following Administration of U3-1402 in Participants with Advanced or Metastatic Colorectal Cancer [4]
    End point description
    The Objective Response Rate (ORR) was defined as the percentage of participants who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), assessed by investigator assessment based on RECIST version 1.1.CR was defined as a reduction of target lesions to non-measurable dimensions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. Confirmed ORR based on investigator assessment is reported and was assessed in the Full Analysis Set.
    End point type
    Secondary
    End point timeframe
    From baseline up to disease progression, death, lost to follow up, or withdrawal of consent by subject (whichever occurs first), up to approximately 16.9 months
    Notes
    [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: Only 1 participant was enrolled into cohort 2, data for this one participant was presented descriptively and was not summarized in aggregated form.
    End point values
    Cohort 1: HER3 High (IHC 3+, 2+)
    Number of subjects analysed
    39
    Units: Percentage of Participants
        number (confidence interval 95%)
    5.1 (0.6 to 17.3)
    No statistical analyses for this end point

    Secondary: Disease Control Rate (DCR) Based on Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 in Participants with Advanced or Metastatic Colorectal Cancer

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    End point title
    Disease Control Rate (DCR) Based on Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 in Participants with Advanced or Metastatic Colorectal Cancer [5]
    End point description
    Disease Control Rate (DCR) was defined as the proportion of participants who achieved a confirmed best overall response (BOR) of complete response (CR), partial response (PR), or stable disease (SD) as assessed by BICR or Investigator assessment. DCR was assessed in the Full Analysis Set.
    End point type
    Secondary
    End point timeframe
    From baseline up to disease progression by BICR, death, lost to follow up, or withdrawal of consent by subject (whichever occurs first), up to approximately 16.9 months
    Notes
    [5] - 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: Only 1 participant was enrolled into cohort 2, data for this one participant was presented descriptively and was not summarized in aggregated form.
    End point values
    Cohort 1: HER3 High (IHC 3+, 2+)
    Number of subjects analysed
    39
    Units: Percentage of Participants
    number (confidence interval 95%)
        Disease Control Rate based on BICR
    56.4 (39.6 to 72.2)
        Disease Control Rate based on Investigator
    56.4 (39.6 to 72.2)
    No statistical analyses for this end point

    Secondary: Time to Tumor Response (TTR) Based on Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 in Participants with Advanced or Metastatic Colorectal Cancer

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    End point title
    Time to Tumor Response (TTR) Based on Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 in Participants with Advanced or Metastatic Colorectal Cancer [6]
    End point description
    Time to Tumor Response (TTR) was defined as the time from the start of study treatment to the date of the first documentation of objective response (CR or PR) that is subsequently confirmed. TTR based on BICR and Investigator assessment is reported and was calculated for responders only.
    End point type
    Secondary
    End point timeframe
    From baseline up to disease progression by BICR, death, lost to follow up, or withdrawal of consent by subject (whichever occurs first), up to approximately 16.9 months
    Notes
    [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: Only 1 participant was enrolled into cohort 2, data for this one participant was presented descriptively and was not summarized in aggregated form.
    End point values
    Cohort 1: HER3 High (IHC 3+, 2+)
    Number of subjects analysed
    2
    Units: months
    median (full range (min-max))
        Time to Tumor Response based on BICR
    1.99 (1.4 to 2.6)
        Time to Tumor Response based on Investigator
    1.53 (1.4 to 1.6)
    No statistical analyses for this end point

    Secondary: Progression-free Survival (PFS) Based on Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 in Participants with Advanced or Metastatic Colorectal Cancer

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    End point title
    Progression-free Survival (PFS) Based on Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 in Participants with Advanced or Metastatic Colorectal Cancer [7]
    End point description
    Progression-free survival (PFS) was defined as the time from the date of enrollment to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. PFS was assessed in the Full Analysis Set.
    End point type
    Secondary
    End point timeframe
    From baseline until disease progression by BICR, death, lost to follow up, or withdrawal of consent by subject (whichever occurs first), up to approximately 16.9 months
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only 1 participant was enrolled into cohort 2, data for this one participant was presented descriptively and was not summarized in aggregated form.
    End point values
    Cohort 1: HER3 High (IHC 3+, 2+)
    Number of subjects analysed
    39
    Units: months
    median (confidence interval 95%)
        Progression Free Survival based on BICR
    2.27 (1.51 to 2.96)
        Progression Free Survival based on Investigator
    2.53 (1.64 to 3.71)
    No statistical analyses for this end point

    Secondary: Overall Survival (OS) Following Administration of U3-1402 in Participants with Advanced or Metastatic Colorectal Cancer

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    End point title
    Overall Survival (OS) Following Administration of U3-1402 in Participants with Advanced or Metastatic Colorectal Cancer [8]
    End point description
    Overall survival (OS) was defined as the time from the date of first dose of study drug to the date of death due to any cause. OS was assessed in the Full Analysis Set.
    End point type
    Secondary
    End point timeframe
    From baseline up to the date of death due to any cause, up to 16.9 months
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only 1 participant was enrolled into cohort 2, data for this one participant was presented descriptively and was not summarized in aggregated form.
    End point values
    Cohort 1: HER3 High (IHC 3+, 2+)
    Number of subjects analysed
    39
    Units: months
        median (confidence interval 95%)
    10.58 (5.36 to 12.09)
    No statistical analyses for this end point

    Secondary: Summary of Treatment Emergent Adverse Events (TEAEs) Following Administration of U3-1402 in Participants with Advanced or Metastatic Colorectal Cancer

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    End point title
    Summary of Treatment Emergent Adverse Events (TEAEs) Following Administration of U3-1402 in Participants with Advanced or Metastatic Colorectal Cancer
    End point description
    A Treatment Emergent Adverse Events (TEAEs) was defined as an adverse event with start or worsening date from the first dose date of the study drug to 47 days after the last dose date of the study drug. TEAEs, study drug-related TEAEs, serious TEAEs, study drug-related TEAEs, and any Adverse Events of Special Interests (AESIs) are presented and were assessed in the Safety Analysis Set.
    End point type
    Secondary
    End point timeframe
    From the signing of the main ICF to 47 days after the last dose of study drug, up to approximately 16.9 months
    End point values
    Cohort 1 & 2: HER3 High (IHC 3+, 2+) & HER3 Low/Negative (IHC)
    Number of subjects analysed
    Units: Count of Participants
    number (not applicable)
        TEAEs
    40
        Study drug-related TEAE
    37
        Serious TEAE (SAE)
    17
        Study drug-related SAE
    9
        Any AESI
    2
        Adjudicated Interstitial Lung Disease (ILD)
    2
        Adjudicated Drug-Related Interstitial Lung Disease
    2
    No statistical analyses for this end point

    Secondary: Number of Participants With HER3 Protein Expression Based on Immunohistochemistry (IHC) Assay

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    End point title
    Number of Participants With HER3 Protein Expression Based on Immunohistochemistry (IHC) Assay [9]
    End point description
    (HER3) protein expression will be measured by an investigational device (HER3 immunohistochemistry [IHC] assay). There is no scoring algorithm developed for the HER3 IHC assay in colon cancer; therefore, the American Society of Clinical Oncology guidelines for HER2 gastric cancer scoring were adopted for use in this study.
    End point type
    Secondary
    End point timeframe
    At Baseline (archival and pre-treatment tumor biopsy) and at Cycle 2
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only 1 participant was enrolled into cohort 2, data for this one participant was presented descriptively and was not summarized in aggregated form.
    End point values
    Cohort 1: HER3 High (IHC 3+, 2+)
    Number of subjects analysed
    39
    Units: Count of Participants
    number (not applicable)
        Archival: 0
    0
        Archival: 1+
    0
        Archival: 2+
    12
        Archival: 3+
    14
        Pre-treatment: 0
    0
        Pre-treatment: 1+
    0
        Pre-treatment: 2+
    3
        Pre-treatment: 3+
    36
        On-treatment: 0
    2
        On-treatment: 1+
    0
        On-treatment: 2+
    6
        On-treatment: 3+
    6
    No statistical analyses for this end point

    Secondary: Percentage of Participants Who Are Anti-Drug Antibody (ADA)-Positive

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    End point title
    Percentage of Participants Who Are Anti-Drug Antibody (ADA)-Positive [10]
    End point description
    Participants who are Anti-Drug Antibody (ADA)-Positive were defined as any participant having a confirmed positive ADA sample at any point in time. ADA titer will be determined for confirmed ADA-positive samples and assessed in the Full Analysis Set.
    End point type
    Secondary
    End point timeframe
    From the start of study treatment to the end of treatment, up to approximately 16.9 months
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only 1 participant was enrolled into cohort 2, data for this one participant was presented descriptively and was not summarized in aggregated form.
    End point values
    Cohort 1: HER3 High (IHC 3+, 2+)
    Number of subjects analysed
    39
    Units: Percentage of Participants
        number (not applicable)
    0
    No statistical analyses for this end point

    Secondary: Percentage of Participants Who Have Treatment Emergent Anti-Drug Antibody (ADA)

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    End point title
    Percentage of Participants Who Have Treatment Emergent Anti-Drug Antibody (ADA) [11]
    End point description
    Participants who are Treatment Emergent Anti-Drug Antibody (ADA) positive will be assessed in the Full Analysis Set.
    End point type
    Secondary
    End point timeframe
    From the start of study treatment to the end of treatment, up to approximately 16.9 months
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only 1 participant was enrolled into cohort 2, data for this one participant was presented descriptively and was not summarized in aggregated form.
    End point values
    Cohort 1: HER3 High (IHC 3+, 2+)
    Number of subjects analysed
    39
    Units: Percentage of Participants
        number (not applicable)
    0
    No statistical analyses for this end point

    Secondary: Maximum Serum Concentration (Cmax) of U3-1402 and Total Anti-HER3 Following Administration of U3-1402 in Participants with Advanced or Metastatic Colorectal Cancer

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    End point title
    Maximum Serum Concentration (Cmax) of U3-1402 and Total Anti-HER3 Following Administration of U3-1402 in Participants with Advanced or Metastatic Colorectal Cancer [12]
    End point description
    Maximum Plasma Concentration (Cmax) was defined as the maximum observed plasma concentration and was calculated using non-compartmental analysis. Cmax for U3-1402 and Total Anti-HER3 are presented and was assessed in the Pharmacokinetic Analysis Set. Cmax was evaluated at select time points.
    End point type
    Secondary
    End point timeframe
    Cycle 1 & 3: Day(D)1 (Before Infusion [BI] & End of Infusion [EOI]), D8, D15; Cycle 2: D1 (BI & EOI), D3, D15; Cycle 4 and thereafter: BI & EOI; End of Treatment; 3 month Follow-up
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only 1 participant was enrolled into cohort 2, data for this one participant was presented descriptively and was not summarized in aggregated form.
    End point values
    Cohort 1: HER3 High (IHC 3+, 2+)
    Number of subjects analysed
    39 [13]
    Units: ug/mL
    arithmetic mean (standard deviation)
        Cycle 1: U3-1402
    155.67 ± 43.453
        Cycle 3: U3-1402
    159.80 ± 47.943
        Cycle 1: Total Anti-HER3
    154.08 ± 32.816
        Cycle 3: Total Anti-HER3
    153.86 ± 39.313
    Notes
    [13] - Cycle 3: U3-1402, n=24; Cycle 3: Total Anti-HER3, n=24
    No statistical analyses for this end point

    Secondary: Maximum Serum Concentration (Cmax) of MAAA-1181 Following Administration of U3-1402 in Participants with Advanced or Metastatic Colorectal Cancer

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    End point title
    Maximum Serum Concentration (Cmax) of MAAA-1181 Following Administration of U3-1402 in Participants with Advanced or Metastatic Colorectal Cancer [14]
    End point description
    Maximum Serum Concentration (Cmax) was defined as the maximum observed serum concentration and was calculated using non-compartmental analysis. Cmax was assessed in the Pharmacokinetic Analysis Set. Cmax was evaluated at select time points.
    End point type
    Secondary
    End point timeframe
    Cycle 1 & 3: Day(D)1 (Before Infusion [BI] & End of Infusion [EOI]), D8, D15; Cycle 2: D1 (BI & EOI), D3, D15; Cycle 4 and thereafter: BI & EOI; End of Treatment; 3 month Follow-up
    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: Only 1 participant was enrolled into cohort 2, data for this one participant was presented descriptively and was not summarized in aggregated form.
    End point values
    Cohort 1: HER3 High (IHC 3+, 2+)
    Number of subjects analysed
    39 [15]
    Units: ng/mL
    geometric mean (standard deviation)
        Cycle 1
    38.09 ± 19.683
        Cycle 3
    16.13 ± 9.292
    Notes
    [15] - Cycle 3, n=24
    No statistical analyses for this end point

    Secondary: Time to Reach Maximum Serum Concentration (Tmax) of U31402, Total Anti-HER3, and MAAA-1181 Following Administration of U3-1402 in Participants with Advanced or Metastatic Colorectal Cancer

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    End point title
    Time to Reach Maximum Serum Concentration (Tmax) of U31402, Total Anti-HER3, and MAAA-1181 Following Administration of U3-1402 in Participants with Advanced or Metastatic Colorectal Cancer [16]
    End point description
    Time of Maximum Serum Concentration (Tmax) was defined as the time of maximum observed serum concentration and was calculated using non-compartmental analysis. Tmax for U3-1402, Total Anti-HER3, and MAAA-1181 are presented and was assessed in the Pharmacokinetic Analysis Set. Tmax was evaluated at select time points.
    End point type
    Secondary
    End point timeframe
    Cycle 1 & 3: Day(D)1 (Before Infusion [BI] & End of Infusion [EOI]), D8, D15; Cycle 2: D1 (BI & EOI), D3, D15; Cycle 4 and thereafter: BI & EOI; End of Treatment; 3 month Follow-up
    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: Only 1 participant was enrolled into cohort 2, data for this one participant was presented descriptively and was not summarized in aggregated form.
    End point values
    Cohort 1: HER3 High (IHC 3+, 2+)
    Number of subjects analysed
    39 [17]
    Units: hours
    median (full range (min-max))
        Cycle 1: U3-1402
    2.42 (1.52 to 5.67)
        Cycle 3: U3-1402
    4.39 (0.53 to 8.78)
        Cycle 1: Total Anti-HER3
    1.72 (1.45 to 505.50)
        Cycle 3: Total Anti-HER3
    3.86 (0.53 to 8.78)
        Cycle 1: MAAA-1181
    5.28 (2.57 to 9.47)
        Cycle 3: MAAA-1181
    4.45 (0.65 to 8.33)
    Notes
    [17] - Cycle 3: U3-1402, Total-Anti-HER3, and MAAA-1181, n=24
    No statistical analyses for this end point

    Secondary: Trough Serum Concentration (Ctrough) of U3-1402 and Total Anti-HER3 Following Administration of U3-1402 in Participants with Advanced or Metastatic Colorectal Cancer

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    End point title
    Trough Serum Concentration (Ctrough) of U3-1402 and Total Anti-HER3 Following Administration of U3-1402 in Participants with Advanced or Metastatic Colorectal Cancer [18]
    End point description
    Trough Serum Concentration (Ctrough) was calculated using non-compartmental analysis. Ctrough for U3-1402 and Total Anti-HER3 are presented and was assessed in the Pharmacokinetic Analysis Set. Ctrough was evaluated at select time points.
    End point type
    Secondary
    End point timeframe
    Cycle 1 & 3: Day(D)1 (Before Infusion [BI] & End of Infusion [EOI]), D8, D15; Cycle 2: D1 (BI & EOI), D3, D15; Cycle 4 and thereafter: BI & EOI; End of Treatment; 3 month Follow-up
    Notes
    [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only 1 participant was enrolled into cohort 2, data for this one participant was presented descriptively and was not summarized in aggregated form.
    End point values
    Cohort 1: HER3 High (IHC 3+, 2+)
    Number of subjects analysed
    39 [19]
    Units: ug/mL
    arithmetic mean (standard deviation)
        Cycle 1: U3-1402
    7.98 ± 24.200
        Cycle 3: U3-1402
    12.76 ± 9.185
        Cycle 1: Anti-Total HER3
    8.55 ± 29.614
        Cycle 3: Anti-Total HER3
    11.49 ± 9.254
    Notes
    [19] - Cycle 1: U3-1402 & Total Anti-HER3, n=35; Cycle 3: U3-1402 & Total Anti-HER3, n=15
    No statistical analyses for this end point

    Secondary: Trough Serum Concentration (Ctrough) of MAAA-1181 Following Administration in Participants with Advanced or Metastatic Colorectal Cancer

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    End point title
    Trough Serum Concentration (Ctrough) of MAAA-1181 Following Administration in Participants with Advanced or Metastatic Colorectal Cancer [20]
    End point description
    Trough Serum Concentration (Ctrough) was calculated using non-compartmental analysis. Ctrough is presented and was assessed in the Pharmacokinetic Analysis Set. Ctrough was evaluated at select time points.
    End point type
    Secondary
    End point timeframe
    Cycle 1 & 3: Day(D)1 (Before Infusion [BI] & End of Infusion [EOI]), D8, D15; Cycle 2: D1 (BI & EOI), D3, D15; Cycle 4 and thereafter: BI & EOI; End of Treatment; 3 month Follow-up
    Notes
    [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only 1 participant was enrolled into cohort 2, data for this one participant was presented descriptively and was not summarized in aggregated form.
    End point values
    Cohort 1: HER3 High (IHC 3+, 2+)
    Number of subjects analysed
    39 [21]
    Units: ng/mL
    arithmetic mean (standard deviation)
        Cycle 1
    0.49 ± 1.423
        Cycle 3
    0.68 ± 0.661
    Notes
    [21] - Cycle 1, n=35; Cycle 3, n=16
    No statistical analyses for this end point

    Secondary: Area Under the Serum Concentration-Time Curve up to Last Quantifiable Time (AUClast) and During Dosing Interval (AUCtau) of U3-1402 and Total Anti-HER3 Following Administration in Participants with Advanced or Metastatic Colorectal Cancer

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    End point title
    Area Under the Serum Concentration-Time Curve up to Last Quantifiable Time (AUClast) and During Dosing Interval (AUCtau) of U3-1402 and Total Anti-HER3 Following Administration in Participants with Advanced or Metastatic Colorectal Cancer [22]
    End point description
    Area under the concentration versus-time curve from time 0 to the last quantifiable concentration (AUClast) and during the dosing interval (AUCtau) was calculated using non-compartmental analysis. AUClast and AUCtau for U3-1402 and Total Anti-HER3 are presented and was assessed in the Pharmacokinetic Analysis Set at select time points.
    End point type
    Secondary
    End point timeframe
    Cycle 1 & 3: Day(D)1 (Before Infusion [BI] & End of Infusion [EOI]), D8, D15; Cycle 2: D1 (BI & EOI), D3, D15; Cycle 4 and thereafter: BI & EOI; End of Treatment; 3 month Follow-up
    Notes
    [22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only 1 participant was enrolled into cohort 2, data for this one participant was presented descriptively and was not summarized in aggregated form.
    End point values
    Cohort 1: HER3 High (IHC 3+, 2+)
    Number of subjects analysed
    39 [23]
    Units: day*ug/mL
    arithmetic mean (standard deviation)
        Cycle 1: U3-1402 (AUClast)
    562.048 ± 246.928
        Cycle 1: U3-1402 (AUCtau)
    569.412 ± 191.026
        Cycle 3: U3-1402 (AUCtau)
    1230.441 ± 257.077
        Cycle 1: Anti-HER3 (AUClast)
    590.108 ± 279.670
        Cycle 1: Anti-HER3 (AUCtau)
    596.235 ± 217.231
        Cycle 3: Anti-HER3 (AUCtau)
    1104.218 ± 397.927
    Notes
    [23] - C1:U3-1402 & Anti-HER3 (AUClast n=20)&(AUCtau n=18);C3:U3-1402 (AUCtau n=7)&Anti-HER3 (AUCtau n=9)
    No statistical analyses for this end point

    Secondary: Area Under the Serum Concentration-Time Curve up to Last Quantifiable Time (AUClast) and During Dosing Interval (AUCtau) of MAAA-1181 Following Administration in Participants with Advanced or Metastatic Colorectal Cancer

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    End point title
    Area Under the Serum Concentration-Time Curve up to Last Quantifiable Time (AUClast) and During Dosing Interval (AUCtau) of MAAA-1181 Following Administration in Participants with Advanced or Metastatic Colorectal Cancer [24]
    End point description
    Area under the concentration versus-time curve from time 0 to the last quantifiable concentration (AUClast) and during the dosing interval (AUCtau) was calculated using non-compartmental analysis. AUClast and AUCtau for MAAA-1181 is presented and was assessed in the Pharmacokinetic Analysis Set at select time points.
    End point type
    Secondary
    End point timeframe
    Cycle 1 & 3: Day(D)1 (Before Infusion [BI] & End of Infusion [EOI]), D8, D15; Cycle 2: D1 (BI & EOI), D3, D15; Cycle 4 and thereafter: BI & EOI; End of Treatment; 3 month Follow-up
    Notes
    [24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only 1 participant was enrolled into cohort 2, data for this one participant was presented descriptively and was not summarized in aggregated form.
    End point values
    Cohort 1: HER3 High (IHC 3+, 2+)
    Number of subjects analysed
    39 [25]
    Units: day*ng/mL
    arithmetic mean (standard deviation)
        Cycle 1: AUClast
    89.963 ± 60.428
        Cycle 1: AUCtau
    92.814 ± 58.939
        Cycle 3: AUCtau
    78.680 ± 34.595
    Notes
    [25] - Cycle 1: AUClast n=20; Cycle 1: AUCtau n=17; Cycle 3 AUCtau n=5
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up 16.9 months.
    Adverse event reporting additional description
    An AE is any untoward medical occurrence in a subject administered a pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    Overall
    Reporting group description
    Participants with high tumor expression & low or negative levels of human epidermal receptor 3 (HER3) low or negative and who received 5.6 mg/Kg of U3-1402 intravenously (IV) on Day 1 of each 21-day cycle (Safety Analysis Set).

    Serious adverse events
    Overall
    Total subjects affected by serious adverse events
         subjects affected / exposed
    17 / 40 (42.50%)
         number of deaths (all causes)
    23
         number of deaths resulting from adverse events
    0
    Investigations
    International normalised ratio increased
         subjects affected / exposed
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nervous system disorders
    Cauda equina syndrome
         subjects affected / exposed
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    2 / 40 (5.00%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    Anaemia
         subjects affected / exposed
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    Disease progression
         subjects affected / exposed
    3 / 40 (7.50%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    2 / 40 (5.00%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Nausea
         subjects affected / exposed
    2 / 40 (5.00%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Rectal obstruction
         subjects affected / exposed
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hepatobiliary disorders
    Biliary obstruction
         subjects affected / exposed
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hyperbilirubinaemia
         subjects affected / exposed
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Dyspnoea
         subjects affected / exposed
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonitis
         subjects affected / exposed
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    2 / 40 (5.00%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Cytomegalovirus infection
         subjects affected / exposed
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Liver abscess
         subjects affected / exposed
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metabolism and nutrition disorders
    Hypokalaemia
         subjects affected / exposed
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Overall
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    40 / 40 (100.00%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    3 / 40 (7.50%)
         occurrences all number
    3
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    24 / 40 (60.00%)
         occurrences all number
    30
    Oedema peripheral
         subjects affected / exposed
    7 / 40 (17.50%)
         occurrences all number
    7
    Pyrexia
         subjects affected / exposed
    4 / 40 (10.00%)
         occurrences all number
    4
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    4 / 40 (10.00%)
         occurrences all number
    5
    Dyspnoea
         subjects affected / exposed
    3 / 40 (7.50%)
         occurrences all number
    4
    Epistaxis
         subjects affected / exposed
    2 / 40 (5.00%)
         occurrences all number
    4
    Hiccups
         subjects affected / exposed
    2 / 40 (5.00%)
         occurrences all number
    2
    Pulmonary embolism
         subjects affected / exposed
    2 / 40 (5.00%)
         occurrences all number
    2
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    2 / 40 (5.00%)
         occurrences all number
    2
    Insomnia
         subjects affected / exposed
    2 / 40 (5.00%)
         occurrences all number
    2
    Investigations
    Aspartate aminotransferase increased
         subjects affected / exposed
    2 / 40 (5.00%)
         occurrences all number
    2
    Blood bilirubin increased
         subjects affected / exposed
    2 / 40 (5.00%)
         occurrences all number
    2
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    2 / 40 (5.00%)
         occurrences all number
    2
    Lymphocyte count decreased
         subjects affected / exposed
    8 / 40 (20.00%)
         occurrences all number
    10
    Neutrophil count decreased
         subjects affected / exposed
    14 / 40 (35.00%)
         occurrences all number
    17
    Platelet count decreased
         subjects affected / exposed
    12 / 40 (30.00%)
         occurrences all number
    19
    Weight decreased
         subjects affected / exposed
    2 / 40 (5.00%)
         occurrences all number
    2
    White blood cell count decreased
         subjects affected / exposed
    7 / 40 (17.50%)
         occurrences all number
    8
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    5 / 40 (12.50%)
         occurrences all number
    6
    Headache
         subjects affected / exposed
    4 / 40 (10.00%)
         occurrences all number
    5
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    14 / 40 (35.00%)
         occurrences all number
    18
    Febrile neutropenia
         subjects affected / exposed
    2 / 40 (5.00%)
         occurrences all number
    2
    Neutropenia
         subjects affected / exposed
    3 / 40 (7.50%)
         occurrences all number
    4
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    4 / 40 (10.00%)
         occurrences all number
    4
    Constipation
         subjects affected / exposed
    11 / 40 (27.50%)
         occurrences all number
    11
    Diarrhoea
         subjects affected / exposed
    15 / 40 (37.50%)
         occurrences all number
    17
    Gastrooesophageal reflux disease
         subjects affected / exposed
    4 / 40 (10.00%)
         occurrences all number
    4
    Nausea
         subjects affected / exposed
    22 / 40 (55.00%)
         occurrences all number
    24
    Stomatitis
         subjects affected / exposed
    5 / 40 (12.50%)
         occurrences all number
    5
    Vomiting
         subjects affected / exposed
    13 / 40 (32.50%)
         occurrences all number
    17
    Hepatobiliary disorders
    Hyperbilirubinaemia
         subjects affected / exposed
    4 / 40 (10.00%)
         occurrences all number
    4
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    7 / 40 (17.50%)
         occurrences all number
    7
    Dry skin
         subjects affected / exposed
    2 / 40 (5.00%)
         occurrences all number
    2
    Pruritus
         subjects affected / exposed
    2 / 40 (5.00%)
         occurrences all number
    2
    Rash
         subjects affected / exposed
    8 / 40 (20.00%)
         occurrences all number
    8
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    2 / 40 (5.00%)
         occurrences all number
    2
    Muscular weakness
         subjects affected / exposed
    2 / 40 (5.00%)
         occurrences all number
    2
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    2 / 40 (5.00%)
         occurrences all number
    2
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    17 / 40 (42.50%)
         occurrences all number
    18
    Dehydration
         subjects affected / exposed
    2 / 40 (5.00%)
         occurrences all number
    2
    Hyperglycaemia
         subjects affected / exposed
    2 / 40 (5.00%)
         occurrences all number
    3
    Hypokalaemia
         subjects affected / exposed
    9 / 40 (22.50%)
         occurrences all number
    13
    Hypomagnesaemia
         subjects affected / exposed
    3 / 40 (7.50%)
         occurrences all number
    6
    Hyponatraemia
         subjects affected / exposed
    3 / 40 (7.50%)
         occurrences all number
    3

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    06 Jun 2020
    This amendment provided revisions to the protocol design to enhance subject safety by implementing further guidance related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and also to ensure that subjects with a history of microsatellite instability-high (MSI-H) colorectal cancer have received immune checkpoint inhibitor therapy (if there were no contraindications) prior to enrollment into this study. Other minor editorial changes were provided to enhance clarity.
    24 Aug 2020
    This amendment provided revisions to the protocol design to enhance subject safety by clarifying that membrane transport inhibitors are permitted, and their use will be closely monitored. Other minor editorial changes were provided to enhance clarity.
    24 Nov 2020
    This amendment provided greater uniformity in the enrolled population by ensuring the prior use of a BRAF inhibitor in patients whose tumors expressed a BRAF V600E mutation. It also provided further specification regarding the required antibody washout period, conditions under which tumor assessments should be conducted, screening, rescreening, and study closure procedures. Other minor editorial changes were provided to enhance clarity.

    Interruptions (globally)

    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    03 Feb 2022
    Study was terminated early given the Interim Analysis for Part 1 (signal finding) did not meet pre-specified criteria and will not proceed to Part 2. Sponsor will proceed closing the study.
    -

    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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