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    Clinical Trial Results:
    A Phase II Basket Study of the Oral Selective Pan-FGFR Inhibitor Debio 1347 in Subjects With Solid Tumors Harboring a Fusion of FGFR1, FGFR2 or FGFR3

    Summary
    EudraCT number
    		 2018-003584-53
    Trial protocol
    		 FR   GR   AT   NL   GB   CZ   DK   NO   BG   FI   ES   HR   RO  
    Global end of trial date
    04 Jan 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    19 Jan 2023
    First version publication date
    19 Jan 2023
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    Debio 1347-201
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03834220
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 IND number: 118244
    Sponsors
    Sponsor organisation name
    Debiopharm International S.A.
    Sponsor organisation address
    Chemin Messidor 5-7, Lausanne, Switzerland, CH - 1002
    Public contact
    Clinical Department, Debiopharm International SA, 0041 21 321 01 11, ClinicalTrials@debiopharm.com
    Scientific contact
    Clinical Department, Debiopharm International SA, 0041 21 321 01 11, ClinicalTrials@debiopharm.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
    04 Jan 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    04 Jan 2022
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The main purpose of this study was to assess the efficacy of Debio 1347 in terms of objective response rate (ORR) in subjects with solid tumors harboring fibroblast growth factor receptor (FGFR) 1-3 gene fusion/rearrangement.
    Protection of trial subjects
    All study subjects were required to read and sign an informed consent form (ICF).
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    22 Mar 2019
    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
    Norway: 1
    Country: Number of subjects enrolled
    Spain: 5
    Country: Number of subjects enrolled
    United Kingdom: 1
    Country: Number of subjects enrolled
    Bulgaria: 1
    Country: Number of subjects enrolled
    Denmark: 1
    Country: Number of subjects enrolled
    Finland: 2
    Country: Number of subjects enrolled
    France: 6
    Country: Number of subjects enrolled
    United States: 39
    Country: Number of subjects enrolled
    Korea, Republic of: 2
    Country: Number of subjects enrolled
    Singapore: 2
    Country: Number of subjects enrolled
    Australia: 1
    Country: Number of subjects enrolled
    Russian Federation: 1
    Country: Number of subjects enrolled
    Taiwan: 1
    Worldwide total number of subjects
    63
    EEA total number of subjects
    16
    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)
    40
    From 65 to 84 years
    23
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 A total of 63 subjects were enrolled at 31 investigational sites in the United States, France, Spain, Finland, Korea, Singapore, Australia, Bulgaria, Denmark, Norway, Russian Federation, Taiwan, and the United Kingdom from 22 March 2019 to 04 January 2022.

    Pre-assignment
    Screening details
    		 A total of 63 subjects with solid tumors harboring FGFR1-3 gene fusion/rearrangement were enrolled into one of the 3 cohorts: Cohort 1: Biliary Tract Cancer (N=30), Cohort 2: Urothelial Cancer (N=4), Cohort 3: All Other Solid Tumor Histologies (N=29) to receive Debio 1347.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Cohort 1: Debio 1347 (Biliary Tract Cancer)
    Arm description
    		 Subjects with biliary tract cancer were included in this cohort to receive Debio 1347 80 milligrams (mg) tablets, orally, once daily (QD), from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median of 20 weeks).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Debio 1347
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Debio 1347 tablets administered orally from Day 1 to Day 28 in 28-day cycles.

    Arm title
    		 Cohort 2: Debio 1347 (Urothelial Cancer)
    Arm description
    		 Subjects with urothelial cancer were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median of 5.86 weeks).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Debio 1347
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Debio 1347 tablets administered orally from Day 1 to Day 28 in 28-day cycles.

    Arm title
    		 Cohort 3: Debio 1347 (All Other Solid Tumor Histologies)
    Arm description
    		 Subjects with all other solid tumor histologies were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median of 8.14 weeks).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Debio 1347
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Debio 1347 tablets administered orally from Day 1 to Day 28 in 28-day cycles.

    Number of subjects in period 1
    		Cohort 1: Debio 1347 (Biliary Tract Cancer) Cohort 2: Debio 1347 (Urothelial Cancer) Cohort 3: Debio 1347 (All Other Solid Tumor Histologies)
    Started
    30
    4
    29
    Completed
    0
    0
    0
    Not completed
    30
    4
    29
         Withdrawal of Consent
    2
    2
    2
         Adverse Event
    1
    -
    -
         Death
    8
    1
    17
         Radiological Disease Progression
    1
    -
    -
         Reason not Specified
    9
    -
    6
         Sponsor/EthicsCommittee Decided to Terminate Study
    9
    1
    4

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Cohort 1: Debio 1347 (Biliary Tract Cancer)
    Reporting group description
    		 Subjects with biliary tract cancer were included in this cohort to receive Debio 1347 80 milligrams (mg) tablets, orally, once daily (QD), from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median of 20 weeks).

    Reporting group title
    Cohort 2: Debio 1347 (Urothelial Cancer)
    Reporting group description
    		 Subjects with urothelial cancer were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median of 5.86 weeks).

    Reporting group title
    Cohort 3: Debio 1347 (All Other Solid Tumor Histologies)
    Reporting group description
    		 Subjects with all other solid tumor histologies were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median of 8.14 weeks).

    Reporting group values
    		 Cohort 1: Debio 1347 (Biliary Tract Cancer) Cohort 2: Debio 1347 (Urothelial Cancer) Cohort 3: Debio 1347 (All Other Solid Tumor Histologies) Total
    Number of subjects
    		 30 4 29 63
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 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)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 59.1 ( 12.21 ) 55.3 ( 15.22 ) 60.0 ( 12.58 ) -
    Gender categorical
    Units: Subjects
        Female
    		 16 2 16 34
        Male
    		 14 2 13 29
    Race
    Units: Subjects
        White
    		 20 3 22 45
        Black or African American
    		 5 0 0 5
        Asian
    		 3 1 2 6
        Not Willing to Provide
    		 1 0 3 4
        Other
    		 1 0 2 3
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 1 0 1 2
        Not Hispanic or Latino
    		 29 4 28 61

    End points

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    End points reporting groups
    Reporting group title
    Cohort 1: Debio 1347 (Biliary Tract Cancer)
    Reporting group description
    		 Subjects with biliary tract cancer were included in this cohort to receive Debio 1347 80 milligrams (mg) tablets, orally, once daily (QD), from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median of 20 weeks).

    Reporting group title
    Cohort 2: Debio 1347 (Urothelial Cancer)
    Reporting group description
    		 Subjects with urothelial cancer were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median of 5.86 weeks).

    Reporting group title
    Cohort 3: Debio 1347 (All Other Solid Tumor Histologies)
    Reporting group description
    		 Subjects with all other solid tumor histologies were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median of 8.14 weeks).

    Primary: Objective Response Rate (ORR) as Centrally Measured by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Criteria

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    End point title
    		 Objective Response Rate (ORR) as Centrally Measured by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Criteria [1]
    End point description
    ORR was defined as the percentage of subjects with a best overall response (BOR) of partial or complete response (PR or CR). BOR was defined as the best confirmed response observed from first administration of study drug until disease progression. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The Intent-to-treat (ITT) Population consisted of all subjects who received study drug. Number of subjects analysed is the number of subjects with measurable disease and tumor assessment at Baseline.
    End point type
    Primary
    End point timeframe
    Up to disease progression or end of study (up to approximately 3 years)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive statistics was planned to be reported for this endpoint.
    End point values
    		 Cohort 1: Debio 1347 (Biliary Tract Cancer) Cohort 2: Debio 1347 (Urothelial Cancer) Cohort 3: Debio 1347 (All Other Solid Tumor Histologies)
    Number of subjects analysed
    30
    3
    25
    Units: percentage of subjects
        number (confidence interval 90%)
    6.7 (1.2 to 19.5)
    0.0 (0.0 to 63.2)
    4.0 (0.2 to 17.6)
    No statistical analyses for this end point

    Secondary: Duration of Response (DOR)

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    End point title
    		 Duration of Response (DOR)
    End point description
    DOR was defined as the time from the date of the initial PR or CR to date of the first documented progression or death due to any cause. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The ITT population consisted of all subjects who received study drug. Only subjects with best overall response of CR or PR were analysed for this endpoint. '9999' signifies that median, lower and upper limit of 95% confidence interval (CI) were not estimable due to low number of subjects with event.
    End point type
    Secondary
    End point timeframe
    Up to disease progression or end of study (up to approximately 3 years)
    End point values
    		 Cohort 1: Debio 1347 (Biliary Tract Cancer) Cohort 2: Debio 1347 (Urothelial Cancer) Cohort 3: Debio 1347 (All Other Solid Tumor Histologies)
    Number of subjects analysed
    0 [2]
    0 [3]
    1
    Units: months
        median (confidence interval 95%)
    ( to )
    ( to )
    5.55 (-9999 to 9999)
    Notes
    [2] - Due to limitation of responders and shortened observation time,interpretable data was not collected.
    [3] - Due to limitation of responders and shortened observation time,interpretable data was not collected.
    No statistical analyses for this end point

    Secondary: Disease Control Rate (DCR)

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    End point title
    		 Disease Control Rate (DCR)
    End point description
    DCR was defined as the percentage of subjects with a BOR of confirmed CR, confirmed PR or stable disease (SD) ≥6 weeks. BOR was defined as the best confirmed response observed from first administration of study drug until disease progression. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. ITT population consisted of all subjects who received study drug.
    End point type
    Secondary
    End point timeframe
    Up to disease progression or end of study (up to approximately 3 years)
    End point values
    		 Cohort 1: Debio 1347 (Biliary Tract Cancer) Cohort 2: Debio 1347 (Urothelial Cancer) Cohort 3: Debio 1347 (All Other Solid Tumor Histologies)
    Number of subjects analysed
    30
    4
    29
    Units: percentage of subjects
        number (confidence interval 95%)
    63.3 (43.9 to 80.1)
    0.0 (0.0 to 60.2)
    34.5 (17.9 to 54.3)
    No statistical analyses for this end point

    Secondary: Progression-Free Survival (PFS)

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    End point title
    		 Progression-Free Survival (PFS)
    End point description
    PFS was defined as the time from the start date of treatment to date of the first documented progression or death due to any cause. ITT population consisted of all subjects who received study drug. '9999' signifies that the upper limit of 95% CI was not estimable due to low number of subjects with event.
    End point type
    Secondary
    End point timeframe
    Up to disease progression or end of study (up to approximately 3 years)
    End point values
    		 Cohort 1: Debio 1347 (Biliary Tract Cancer) Cohort 2: Debio 1347 (Urothelial Cancer) Cohort 3: Debio 1347 (All Other Solid Tumor Histologies)
    Number of subjects analysed
    30
    4
    29
    Units: months
        median (confidence interval 95%)
    3.68 (3.55 to 10.58)
    1.77 (0.95 to 9999)
    1.84 (1.71 to 3.52)
    No statistical analyses for this end point

    Secondary: Overall Survival (OS)

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    End point title
    		 Overall Survival (OS)
    End point description
    OS was defined as defined as the time from the start date of treatment to date of death due to any cause. ITT population consisted of all subjects who received study drug. '9999' signifies that median, lower and upper limit of 95% CI were not estimable due to low number of subjects with events.
    End point type
    Secondary
    End point timeframe
    Until death or loss to follow-up or end of study (up to approximately 3 years)
    End point values
    		 Cohort 1: Debio 1347 (Biliary Tract Cancer) Cohort 2: Debio 1347 (Urothelial Cancer) Cohort 3: Debio 1347 (All Other Solid Tumor Histologies)
    Number of subjects analysed
    30
    4
    29
    Units: months
        median (confidence interval 95%)
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    7.13 (4.30 to 11.37)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Treatment-Emergent Adverse Events (TEAEs) Assessed by National Cancer Institute Common Terminology Criteria (NCI CTCAE) v5.0 and Serious Adverse Events (SAEs)

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    End point title
    		 Percentage of Subjects With Treatment-Emergent Adverse Events (TEAEs) Assessed by National Cancer Institute Common Terminology Criteria (NCI CTCAE) v5.0 and Serious Adverse Events (SAEs)
    End point description
    An AE is any untoward medical occurrence in a subject or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. A TEAE is defined as an AE that either starts or worsens in severity on or after the first administration of the study drug and within 30 days of the last administration of the study drug. An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. Safety Population consisted of all subjects who received study drug.
    End point type
    Secondary
    End point timeframe
    From first dose of study drug up to 30 days post last dose (Up to approximately 3 years)
    End point values
    		 Cohort 1: Debio 1347 (Biliary Tract Cancer) Cohort 2: Debio 1347 (Urothelial Cancer) Cohort 3: Debio 1347 (All Other Solid Tumor Histologies)
    Number of subjects analysed
    30
    4
    29
    Units: percentage of subjects
    number (not applicable)
        TEAEs
    100.0
    100.0
    96.6
        Serious TEAEs
    46.7
    50.0
    24.1
    No statistical analyses for this end point

    Secondary: Trough Concentration at Steady State (Ctrough,ss) of Debio 1347 in Plasma

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    End point title
    		 Trough Concentration at Steady State (Ctrough,ss) of Debio 1347 in Plasma
    End point description
    Geometric coefficient of variation (CV) reported in this endpoint is geometric CV%. The Pharmacokinetic (PK) Population included subjects who received one or more doses of Debio 1347 and have at least one PK concentration result available. Number of subjects analysed is the number of subjects with data available for analyses.
    End point type
    Secondary
    End point timeframe
    Pre-dose on Days 14 and 28, and 1, 3, 7 hours post-dose on Day 28 of Cycle 1; pre-dose on Days 14 and 28, and 3 hours post-dose on Day 28 of Cycle 2
    End point values
    		 Cohort 1: Debio 1347 (Biliary Tract Cancer) Cohort 2: Debio 1347 (Urothelial Cancer) Cohort 3: Debio 1347 (All Other Solid Tumor Histologies)
    Number of subjects analysed
    30
    3
    26
    Units: nanogram per millilitre (ng/mL)
        geometric mean (geometric coefficient of variation)
    619.6 ( 100.0 )
    306.8 ( 43.4 )
    463.2 ( 127.3 )
    No statistical analyses for this end point

    Secondary: Area Under the Plasma Concentration-Time Curve Over the Dosing Interval at Steady State (AUCtau,ss) of Debio 1347 in Plasma

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    End point title
    		 Area Under the Plasma Concentration-Time Curve Over the Dosing Interval at Steady State (AUCtau,ss) of Debio 1347 in Plasma
    End point description
    Geometric CV reported in this endpoint is geometric CV%. PK Population included subjects who received one or more doses of Debio 1347 and have at least one PK concentration result available. Number of subjects analysed is the number of subjects with data available for analyses.
    End point type
    Secondary
    End point timeframe
    Pre-dose on Days 14 and 28, and 1, 3, 7 hours post-dose on Day 28 of Cycle 1; pre-dose on Days 14 and 28, and 3 hours post-dose on Day 28 of Cycle 2
    End point values
    		 Cohort 1: Debio 1347 (Biliary Tract Cancer) Cohort 2: Debio 1347 (Urothelial Cancer) Cohort 3: Debio 1347 (All Other Solid Tumor Histologies)
    Number of subjects analysed
    30
    3
    26
    Units: hour*nanogram (h*ng)/mL
        geometric mean (geometric coefficient of variation)
    23326.7 ( 70.4 )
    13999.0 ( 39.1 )
    18192.1 ( 86.2 )
    No statistical analyses for this end point

    Secondary: Correlation of Debio 1347 Plasma Concentration (C) and QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF)

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    End point title
    		 Correlation of Debio 1347 Plasma Concentration (C) and QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF)
    End point description
    End point type
    Secondary
    End point timeframe
    Pre-dose on Days 14 and 28, and 1, 3, 7 hours post-dose on Day 28 of Cycle 1; pre-dose on Days 14 and 28, and 3 hours post-dose on Day 28 of Cycle 2
    End point values
    		 Cohort 1: Debio 1347 (Biliary Tract Cancer) Cohort 2: Debio 1347 (Urothelial Cancer) Cohort 3: Debio 1347 (All Other Solid Tumor Histologies)
    Number of subjects analysed
    0 [4]
    0 [5]
    0 [6]
    Units: correlation coefficient (r)
        geometric mean (confidence interval 90%)
    ( to )
    ( to )
    ( to )
    Notes
    [4] - Analysis of Debio 1347 C-QTcF relationship was not deemed necessary and was not conducted.
    [5] - Analysis of Debio 1347 C-QTcF relationship was not deemed necessary and was not conducted.
    [6] - Analysis of Debio 1347 C-QTcF relationship was not deemed necessary and was not conducted.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first dose of study drug up to 30 days post last dose (up to approximately 3 years)
    Adverse event reporting additional description
    Safety Population consisted of all subjects who received study drug.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.0
    Reporting groups
    Reporting group title
    Cohort 1: Debio 1347 (Biliary Tract Cancer)
    Reporting group description
    		 Subjects with biliary tract cancer were included in this cohort to receive Debio 1347 80 milligrams (mg) tablets, orally, once daily (QD), from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median of 20 weeks).

    Reporting group title
    Cohort 2: Debio 1347 (Urothelial Cancer)
    Reporting group description
    		 Subjects with urothelial cancer were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median of 5.86 weeks).

    Reporting group title
    Cohort 3: Debio 1347 (All Other Solid Tumor Histologies)
    Reporting group description
    		 Subjects with all other solid tumor histologies were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median of 8.14 weeks).

    Serious adverse events
    		 Cohort 1: Debio 1347 (Biliary Tract Cancer) Cohort 2: Debio 1347 (Urothelial Cancer) Cohort 3: Debio 1347 (All Other Solid Tumor Histologies)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    14 / 30 (46.67%)
    2 / 4 (50.00%)
    7 / 29 (24.14%)
         number of deaths (all causes)
    9
    1
    17
         number of deaths resulting from adverse events
    0
    0
    1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Malignant melanoma
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 4 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tumour pain
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 4 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Hypotension
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 4 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 4 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 4 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Laryngeal haemorrhage
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 4 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 4 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Femur fracture
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 4 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac arrest
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 4 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Nervous system disorders
    Syncope
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 4 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 4 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 4 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 4 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Enterocolitis
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 4 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 4 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 4 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 4 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash maculo-papular
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 4 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    3 / 30 (10.00%)
    0 / 4 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract obstruction
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 4 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 4 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 4 (25.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    1 / 30 (3.33%)
    1 / 4 (25.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Biliary sepsis
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 4 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Biliary tract infection
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 4 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 4 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 4 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 4 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 4 (25.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 4 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 4 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Cohort 1: Debio 1347 (Biliary Tract Cancer) Cohort 2: Debio 1347 (Urothelial Cancer) Cohort 3: Debio 1347 (All Other Solid Tumor Histologies)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    30 / 30 (100.00%)
    4 / 4 (100.00%)
    28 / 29 (96.55%)
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    9 / 30 (30.00%)
    1 / 4 (25.00%)
    10 / 29 (34.48%)
         occurrences all number
    10
    1
    10
    Pyrexia
         subjects affected / exposed
    6 / 30 (20.00%)
    0 / 4 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    7
    0
    1
    Oedema peripheral
         subjects affected / exposed
    3 / 30 (10.00%)
    0 / 4 (0.00%)
    3 / 29 (10.34%)
         occurrences all number
    4
    0
    3
    Asthenia
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 4 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    2
    0
    1
    Pain
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 4 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    2
    0
    1
    Influenza like illness
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 4 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    0
    0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 4 (25.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    4 / 30 (13.33%)
    0 / 4 (0.00%)
    4 / 29 (13.79%)
         occurrences all number
    4
    0
    4
    Epistaxis
         subjects affected / exposed
    4 / 30 (13.33%)
    0 / 4 (0.00%)
    4 / 29 (13.79%)
         occurrences all number
    4
    0
    6
    Oropharyngeal pain
         subjects affected / exposed
    4 / 30 (13.33%)
    0 / 4 (0.00%)
    4 / 29 (13.79%)
         occurrences all number
    4
    0
    4
    Cough
         subjects affected / exposed
    3 / 30 (10.00%)
    1 / 4 (25.00%)
    3 / 29 (10.34%)
         occurrences all number
    3
    1
    3
    Nasal dryness
         subjects affected / exposed
    1 / 30 (3.33%)
    2 / 4 (50.00%)
    2 / 29 (6.90%)
         occurrences all number
    1
    2
    2
    Haemoptysis
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 4 (0.00%)
    3 / 29 (10.34%)
         occurrences all number
    0
    0
    3
    Productive cough
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 4 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    1
    0
    2
    Rhinorrhoea
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 4 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    0
    0
    2
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 4 (0.00%)
    4 / 29 (13.79%)
         occurrences all number
    2
    0
    4
    Depression
         subjects affected / exposed
    1 / 30 (3.33%)
    1 / 4 (25.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    1
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    4 / 30 (13.33%)
    1 / 4 (25.00%)
    4 / 29 (13.79%)
         occurrences all number
    5
    1
    4
    Weight decreased
         subjects affected / exposed
    4 / 30 (13.33%)
    1 / 4 (25.00%)
    2 / 29 (6.90%)
         occurrences all number
    6
    1
    2
    Aspartate aminotransferase increased
         subjects affected / exposed
    3 / 30 (10.00%)
    1 / 4 (25.00%)
    2 / 29 (6.90%)
         occurrences all number
    4
    2
    2
    Blood alkaline phosphatase increased
         subjects affected / exposed
    3 / 30 (10.00%)
    0 / 4 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    5
    0
    1
    Neutrophil count decreased
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 4 (25.00%)
    3 / 29 (10.34%)
         occurrences all number
    0
    1
    3
    Platelet count decreased
         subjects affected / exposed
    3 / 30 (10.00%)
    0 / 4 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    5
    0
    1
    White blood cell count decreased
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 4 (25.00%)
    3 / 29 (10.34%)
         occurrences all number
    0
    1
    5
    Blood bilirubin increased
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 4 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    4
    0
    1
    Blood creatinine increased
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 4 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    1
    0
    3
    Nervous system disorders
    Dysgeusia
         subjects affected / exposed
    7 / 30 (23.33%)
    1 / 4 (25.00%)
    9 / 29 (31.03%)
         occurrences all number
    7
    1
    9
    Dizziness
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 4 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    2
    0
    2
    Headache
         subjects affected / exposed
    3 / 30 (10.00%)
    0 / 4 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    3
    0
    1
    Peripheral sensory neuropathy
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 4 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    3
    0
    1
    Lethargy
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 4 (25.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Taste disorder
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 4 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    0
    0
    2
    Paraesthesia
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 4 (25.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    3 / 30 (10.00%)
    0 / 4 (0.00%)
    9 / 29 (31.03%)
         occurrences all number
    5
    0
    11
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 4 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    0
    0
    Eye disorders
    Dry eye
         subjects affected / exposed
    3 / 30 (10.00%)
    1 / 4 (25.00%)
    7 / 29 (24.14%)
         occurrences all number
    3
    1
    7
    Vision blurred
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 4 (0.00%)
    3 / 29 (10.34%)
         occurrences all number
    1
    0
    3
    Lacrimation increased
         subjects affected / exposed
    1 / 30 (3.33%)
    1 / 4 (25.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    1
    0
    Photophobia
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 4 (25.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    9 / 30 (30.00%)
    0 / 4 (0.00%)
    11 / 29 (37.93%)
         occurrences all number
    11
    0
    12
    Stomatitis
         subjects affected / exposed
    9 / 30 (30.00%)
    2 / 4 (50.00%)
    9 / 29 (31.03%)
         occurrences all number
    17
    2
    9
    Diarrhoea
         subjects affected / exposed
    8 / 30 (26.67%)
    0 / 4 (0.00%)
    10 / 29 (34.48%)
         occurrences all number
    9
    0
    12
    Dry mouth
         subjects affected / exposed
    11 / 30 (36.67%)
    1 / 4 (25.00%)
    6 / 29 (20.69%)
         occurrences all number
    11
    1
    6
    Nausea
         subjects affected / exposed
    10 / 30 (33.33%)
    0 / 4 (0.00%)
    8 / 29 (27.59%)
         occurrences all number
    10
    0
    9
    Vomiting
         subjects affected / exposed
    7 / 30 (23.33%)
    1 / 4 (25.00%)
    7 / 29 (24.14%)
         occurrences all number
    9
    1
    9
    Abdominal pain
         subjects affected / exposed
    6 / 30 (20.00%)
    0 / 4 (0.00%)
    4 / 29 (13.79%)
         occurrences all number
    7
    0
    4
    Gastrooesophageal reflux disease
         subjects affected / exposed
    2 / 30 (6.67%)
    1 / 4 (25.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    1
    0
    Haemorrhoids
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 4 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    2
    0
    1
    Oral pain
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 4 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    1
    0
    2
    Abdominal distension
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 4 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    0
    0
    2
    Hepatobiliary disorders
    Hyperbilirubinaemia
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 4 (0.00%)
    5 / 29 (17.24%)
         occurrences all number
    9
    0
    8
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    14 / 30 (46.67%)
    1 / 4 (25.00%)
    9 / 29 (31.03%)
         occurrences all number
    14
    1
    10
    Dry skin
         subjects affected / exposed
    8 / 30 (26.67%)
    0 / 4 (0.00%)
    6 / 29 (20.69%)
         occurrences all number
    8
    0
    6
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    6 / 30 (20.00%)
    0 / 4 (0.00%)
    5 / 29 (17.24%)
         occurrences all number
    9
    0
    6
    Onychomadesis
         subjects affected / exposed
    3 / 30 (10.00%)
    0 / 4 (0.00%)
    3 / 29 (10.34%)
         occurrences all number
    3
    0
    3
    Rash
         subjects affected / exposed
    1 / 30 (3.33%)
    1 / 4 (25.00%)
    2 / 29 (6.90%)
         occurrences all number
    1
    1
    2
    Skin ulcer
         subjects affected / exposed
    1 / 30 (3.33%)
    1 / 4 (25.00%)
    2 / 29 (6.90%)
         occurrences all number
    1
    1
    2
    Nail discolouration
         subjects affected / exposed
    3 / 30 (10.00%)
    0 / 4 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    3
    0
    0
    Nail disorder
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 4 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    2
    0
    1
    Pruritus
         subjects affected / exposed
    2 / 30 (6.67%)
    1 / 4 (25.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    1
    0
    Rash maculo-papular
         subjects affected / exposed
    3 / 30 (10.00%)
    0 / 4 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    3
    0
    0
    Onycholysis
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 4 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    0
    0
    Pain of skin
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 4 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    4
    0
    0
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    1 / 30 (3.33%)
    1 / 4 (25.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    1
    1
    Chronic kidney disease
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 4 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    0
    0
    Musculoskeletal and connective tissue disorders
    Pain in extremity
         subjects affected / exposed
    4 / 30 (13.33%)
    0 / 4 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    6
    0
    2
    Arthralgia
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 4 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    2
    0
    2
    Back pain
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 4 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    1
    0
    3
    Flank pain
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 4 (0.00%)
    3 / 29 (10.34%)
         occurrences all number
    0
    0
    3
    Muscle spasms
         subjects affected / exposed
    2 / 30 (6.67%)
    1 / 4 (25.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    1
    0
    Musculoskeletal pain
         subjects affected / exposed
    3 / 30 (10.00%)
    0 / 4 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    3
    0
    0
    Myalgia
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 4 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    0
    0
    2
    Infections and infestations
    Paronychia
         subjects affected / exposed
    6 / 30 (20.00%)
    0 / 4 (0.00%)
    4 / 29 (13.79%)
         occurrences all number
    6
    0
    4
    Urinary tract infection
         subjects affected / exposed
    3 / 30 (10.00%)
    0 / 4 (0.00%)
    3 / 29 (10.34%)
         occurrences all number
    5
    0
    6
    Nasopharyngitis
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 4 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    1
    0
    2
    Conjunctivitis
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 4 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    0
    0
    Metabolism and nutrition disorders
    Hyperphosphataemia
         subjects affected / exposed
    24 / 30 (80.00%)
    2 / 4 (50.00%)
    22 / 29 (75.86%)
         occurrences all number
    40
    2
    31
    Decreased appetite
         subjects affected / exposed
    5 / 30 (16.67%)
    1 / 4 (25.00%)
    9 / 29 (31.03%)
         occurrences all number
    7
    1
    9
    Hypomagnesaemia
         subjects affected / exposed
    4 / 30 (13.33%)
    0 / 4 (0.00%)
    6 / 29 (20.69%)
         occurrences all number
    5
    0
    7
    Hypophosphataemia
         subjects affected / exposed
    3 / 30 (10.00%)
    1 / 4 (25.00%)
    3 / 29 (10.34%)
         occurrences all number
    3
    1
    3
    Hypercalcaemia
         subjects affected / exposed
    3 / 30 (10.00%)
    0 / 4 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    3
    0
    6
    Hyponatraemia
         subjects affected / exposed
    3 / 30 (10.00%)
    0 / 4 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    3
    0
    1
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 30 (0.00%)
    1 / 4 (25.00%)
    2 / 29 (6.90%)
         occurrences all number
    0
    1
    3
    Hypokalaemia
         subjects affected / exposed
    1 / 30 (3.33%)
    0 / 4 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    1
    0
    2
    Dehydration
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 4 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    0
    0
    2
    Hyperkalaemia
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 4 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    0
    0
    3
    Hypocalcaemia
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 4 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    0
    0
    2

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    17 Dec 2018
    The following changes were implemented with Amendment 1: 1. The Risk-benefit Assessment was added and minor updates were made. 2. Inclusion criteria was updated to reflect that subjects should refrain from donating egg(s) or sperm during clinical trials with Debio 1347 and for a suitable period post-investigational medicinal product (IMP) use. 3. Updated inclusion criteria regarding the maximum total bilirubin level allowed since subjects with cholangiocarcinoma were to be enrolled. 4. Inclusion criteria updated to clearly state that the subjects must have exhausted all lines of standard therapy, unless, for some reason, they are ineligible to it. 5. Inclusion criteria updated to clarify sexual abstinence is only a highly effective method when it is the usual and preferred lifestyle of the subject. 6. Exclusion criterion updated to clarify the chemotherapy or radiotherapy or small molecule anti-cancer agents exclusion criteria. Clarification that Debio 1347 has no potential genotoxicity. 7. Added that the use of proton pump inhibitors has been prohibited. 8. Updated post-study safety reporting language. 9. Added requirement for pregnancy testing in female subjects for 6 months post End of treatment. 10. Added a description of the End-of-study and End of treatment Criteria.
    16 Jul 2020
    The protocol was amended as per Amendment 2 to reflect the changes due to the permanent halt to the enrolment in the study and for all subjects who remained on treatment with Debio 1347 after the implementation of Protocol Amendment 2, the assessments and procedures defined in the study protocol were no longer to be in force and were to be replaced by standard institutional care practice. Subjects were to be followed regularly (at least every 2 months) to assess the potential occurrence of safety event and conduct safety laboratory analysis. Only safety data were to be collected in the electronic case report form (eCRF).

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    17 Jun 2020
    Due to lower efficacy of Debio 1347 observed during initial statistical review of pooled data, the Sponsor decided to permanently halt the enrolment in the study after consultation with the data monitoring committee (DMC).
    -

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Due to the premature termination of subject recruitment and shortened follow up, the primary efficacy analysis was likely underpowered in the final analysis, leading to greater statistical uncertainty in results.
    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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