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    Clinical Trial Results:
    A phase II multicenter, single arm study of oral BGJ398 in adult patients with advanced or metastatic cholangiocarcinoma with FGFR2 gene fusions or other FGFR genetic alterations who failed or are intolerant to platinum-based chemotherapy

    Summary
    EudraCT number
    2013-005085-19
    Trial protocol
    ES   BE   IT   DE   GB  
    Global end of trial date
    07 Feb 2022

    Results information
    Results version number
    v1(current)
    This version publication date
    24 Dec 2023
    First version publication date
    24 Dec 2023
    Other versions
    Summary report(s)
    02. 2204-Abbr CSR_final published_Synopsis_30Jan2023
    CSR Final

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    CBGJ398X2204
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02150967
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    QED Therapeutics, Inc.
    Sponsor organisation address
    1800 Owens Street, Suite C-1200, San Francisco, United States, CA 94158
    Public contact
    David van Veenhuyzen,, QED Therapeutics, Inc., +1 650 296 2307, clinicaltrials@QEDTx.com
    Scientific contact
    David van Veenhuyzen,, QED Therapeutics, Inc., +1 650 296 2307, clinicaltrials@QEDTx.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
    30 Jan 2023
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    01 Mar 2021
    Global end of trial reached?
    Yes
    Global end of trial date
    07 Feb 2022
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To evaluate the efficacy of single agent BGJ398 in patients with advanced or metastatic cholangiocarcinoma with FGFR2 gene fusions/translocations or other FGFR genetic alterations assessed by investigator as per RECIST v1.1.
    Protection of trial subjects
    Prior to the start of the study, the study protocol and Informed Consent Form (ICF) were reviewed and approved by the appropriate EC. All amendments to the protocol were approved by the EC. Subjects signed the pre-screening/generic ICF in the presence of a suitably trained staff member prior to the conduct of pre-screening procedures. Prior to the commencement of the study, each subject was provided with study-specific ICF giving details of the IMPs, procedures and potential risks involved. Study Design: This multicenter, open-label, 3-cohort, Phase 2 study evaluated infigratinib antitumor activity in subjects with advanced or metastatic cholangiocarcinoma with FGFR genetic alterations. Documented evidence of FGFR gene alterations was required for enrollment. The specific genetic alterations allowed on study were determined through molecular prescreening and subdivided into FGFR2 fusions vs other FGFR genetic alterations. This abbreviated CSR provides methods and safety results of the final analyses of the study for Cohorts 1, 2, and 3. Results of the primary efficacy analysis (Cohort 1) are reported in the primary CSR (X2204p]. The Schedule of Assessments used in the study is provided in the primary CSR [X2204p – Section 9.5]. To assess the efficacy of infigratinib, subjects were evaluated for tumor response radiographically every 8 weeks until disease progression using RECIST version 1.1 or until subjects discontinued from the study. Responses of partial response (PR) and complete response (CR) were confirmed by repeat assessment ≥4 weeks after the criterion for response was first met. The safety evaluation was based on adverse event (AE) reporting, laboratory evaluations, vital signs, ophthalmic evaluations, electrocardiogram (ECG) and cardiac imaging assessments, Eastern Cooperative Oncology Group (ECOG) performance status (PS), and pregnancy outcome (if applicable).
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    23 Jul 2014
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Ethical reason
    Long term follow-up duration
    5 Years
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Singapore: 4
    Country: Number of subjects enrolled
    United Kingdom: 4
    Country: Number of subjects enrolled
    United States: 94
    Country: Number of subjects enrolled
    Belgium: 5
    Country: Number of subjects enrolled
    Germany: 18
    Country: Number of subjects enrolled
    Spain: 13
    Country: Number of subjects enrolled
    Korea, Democratic People's Republic of: 1
    Country: Number of subjects enrolled
    Taiwan: 1
    Country: Number of subjects enrolled
    Thailand: 3
    Worldwide total number of subjects
    143
    EEA total number of subjects
    36
    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)
    107
    From 65 to 84 years
    36
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    First participant enrolled: 23 July 2014 Last Patient Last Visit performed 07 February 2022

    Pre-assignment
    Screening details
    Potential participants were approached if they fulfil the inclusion/exclusion criteria and were asked if they would like to participate in the study. Patients were divided into 3 cohorts. Cohort 1 , Cohort 2 and Cohort 3.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Cohort 1
    Arm description
    Subjects with FGFR2 fusions/rearrangements (N=108). These are the same 108 subjects as the main dataset presented in the interim CSR [X2204i] (“Interim Analysis Set 2 for Cohort 1”) and the primary CSR [X2204p] (“subjects with FGFR2 fusion/rearrangement in Cohort 1 FAS”); the only difference between reports was the length of follow-up (an additional 11 months). Note: No new efficacy analysis was done for the final CSR (aCSR), since these subs had completed their primary efficacy analysis (reported into he primary CSR)
    Arm type
    Experimental

    Investigational medicinal product name
    Infigratinib
    Investigational medicinal product code
    BGJ398
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    125 mg milligram(s) per day Oral use

    Arm title
    Cohort 2
    Arm description
    Cohort 2: Subjects with other FGFR alterations other than FGFR2 gene fusions or rearrangements (N=25). This cohort includes all 11 subjects enrolled to Cohort 2 and the 14 subjects with other FGFR alterations enrolled to Cohort 1 under the original protocol. Note: No efficacy analysis were performed since the study was terminated early.
    Arm type
    Experimental

    Investigational medicinal product name
    Infigratinib
    Investigational medicinal product code
    BGJ398
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    125 mg milligram(s) per day Oral use

    Arm title
    Cohort 3
    Arm description
    Cohort 3: Subjects with FGFR2 gene fusions/rearrangements who have received a prior FGFR inhibitor other than infigratinib (N=10). Note that Cohorts 2 and 3 were added at protocol amendment 4 to support exploratory objectives of the study and were not included in the analyses presented in the interim CSR [X2204i] or primary CSR [X2204p].
    Arm type
    Experimental

    Investigational medicinal product name
    Infigratinib
    Investigational medicinal product code
    BGJ398
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    125 mg milligram(s) per day Oral use

    Number of subjects in period 1
    Cohort 1 Cohort 2 Cohort 3
    Started
    108
    25
    10
    Completed
    108
    25
    10

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Cohort 1
    Reporting group description
    Subjects with FGFR2 fusions/rearrangements (N=108). These are the same 108 subjects as the main dataset presented in the interim CSR [X2204i] (“Interim Analysis Set 2 for Cohort 1”) and the primary CSR [X2204p] (“subjects with FGFR2 fusion/rearrangement in Cohort 1 FAS”); the only difference between reports was the length of follow-up (an additional 11 months). Note: No new efficacy analysis was done for the final CSR (aCSR), since these subs had completed their primary efficacy analysis (reported into he primary CSR)

    Reporting group title
    Cohort 2
    Reporting group description
    Cohort 2: Subjects with other FGFR alterations other than FGFR2 gene fusions or rearrangements (N=25). This cohort includes all 11 subjects enrolled to Cohort 2 and the 14 subjects with other FGFR alterations enrolled to Cohort 1 under the original protocol. Note: No efficacy analysis were performed since the study was terminated early.

    Reporting group title
    Cohort 3
    Reporting group description
    Cohort 3: Subjects with FGFR2 gene fusions/rearrangements who have received a prior FGFR inhibitor other than infigratinib (N=10). Note that Cohorts 2 and 3 were added at protocol amendment 4 to support exploratory objectives of the study and were not included in the analyses presented in the interim CSR [X2204i] or primary CSR [X2204p].

    Reporting group values
    Cohort 1 Cohort 2 Cohort 3 Total
    Number of subjects
    108 25 10 143
    Age categorical
    Units: Subjects
        In utero
    0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0 0
        Newborns (0-27 days)
    0 0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0 0
        Children (2-11 years)
    0 0 0 0
        Adolescents (12-17 years)
    0 0 0 0
        Adults (18-64 years)
    82 17 8 107
        From 65-84 years
    26 8 2 36
        85 years and over
    0 0 0 0
    Gender categorical
    Units: Subjects
        Female
    67 12 3 82
        Male
    41 13 7 61
    ECOG PS
    Measure Description: Functional status was assessed at baseline using the Eastern Cooperative Oncology Group Performance Scale (ECOG PS)
    Units: Subjects
        00
    45 11 3 59
        01
    62 13 7 82
        02
    1 1 0 2
    Primary site of cancer
    Primary site of cancer
    Units: Subjects
        Bile duct
    105 24 10 139
        Cholangiocarcinoma
    1 1 0 2
        Liver
    2 0 0 2
    Non-Liver MetastaticSite
    Units: Subjects
        No metastatic site
    5 4 0 9
        Had metastatic site
    102 21 10 133
        Missing
    1 0 0 1
    Histological Grade
    Units: Subjects
        Well differentiated
    9 2 0 11
        Moderately differentiated
    42 14 7 63
        Poorly differentiated
    33 2 2 37
        Undifferentiated
    1 0 0 1
        Unknown/missing
    22 7 1 30
        Not Applicable
    1 0 0 1
    Stage at Time of Study Entry
    The AJCC staging manual (7th edition) for intrahepaticcholangiocarcinoma was used for cancer staging at baseline, defined asfollows: Stage I: solitary tumor without vascular invasion. Stage II: solitary tumor withvascular invasion or multiple tumors with or without vascular invasion. Stage III: tumor perforating the visceral peritoneum or involving local hepaticstructure by direct invasion. Stage IV: tumor with periductal invasion, or any tumor with regional lymph node metastasis present, or any tumor with or without lymph node metastasis but metastasized to a distant site.
    Units: Subjects
        Stage II
    1 3 0 4
        Stage III
    0 2 0 2
        Stage IV
    107 20 10 137
    Best Overall Response (BOR) by Investigator
    BOR is defined as the best overall response a subject achieved during the study before any subsequent antineoplastic therapy. The endpoint is summarized for the rate of BOR of CR, PR, progressive disease(PD), and stable disease (SD), evaluated by CT or MRI scans every 28 days. Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusion) Overall Number of Participants Analyzed 108
    Units: Subjects
        Confirmed CR
    0 0 0 0
        Confirmed PR
    35 0 0 35
        Stable Disease
    56 0 0 56
        Progressive Disease
    11 0 0 11
        Not Done
    6 25 10 41
    Retrospective Analysis of Post-second-line Antineoplastic Treatment Outcomes on BOR - After 2nd line
    Post-hoc subgroup assessment of efficacy in those subjects who were receiving infigratinib as a third or later line of treatment. Note: The primary efficacy outcome measures were prespecified only for Cohort 1 Analyzed 59
    Units: Subjects
        Complete response
    0 0 0 0
        Partial response
    0 0 0 0
        Stable disease
    19 0 0 19
        Progressive disease
    22 0 0 22
        Unknown
    18 0 0 18
        Not done
    49 25 10 84
    Retrospective Analysis of Post-second-line Antineoplastic Treatment Outcomes on BOR - 3rd or later
    Post-hoc subgroup assessment of efficacy in those subjects who were receiving infigratinib as a third or later line of treatment. Note: The primary efficacy outcome measures were prespecified only for Cohort 1 Analyzed: 59
    Units: Subjects
        Complete response
    0 0 0 0
        Partial response
    17 0 0 17
        Stable disease
    31 0 0 31
        Progressive disease
    7 0 0 7
        Unknown
    0 0 0 0
        Not done
    53 25 10 88
    Overall Response Rate (ORR) as Assessed by Blinded Independent Central Imaging Review (BICR)
    ORR is defined as the percentage (%) of subjects with a best overall response of Complete Response(CR) or Partial Response (PR), as per Response Evaluation Criteria in Solid Tumors (RECIST), Version1.1, evaluated by computed tomography (CT) or magnetic resonance imaging (MRI) scans every 28 days. Due to early termination of the study, no formal efficacy analyses were performed for Cohorts 2 and 3. Overall Number of Participants Analyzed 108
    Units: Percentage (%)of subjects with CR or PR
        median (full range (min-max))
    23.1 (15.6 to 32.2) 0 (0 to 0) 0 (0 to 0) -
    Disease Control Rate (DCR) by BICR
    DCR is the percentage (%) of subjects with a BOR of CR, PR, or SD, evaluated by CT or MRI scans every 28 days. Results are based on both BICR and on Investigator assessment. Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusions)
    Units: Percentage (%) with CR, PR, or SD
        median (full range (min-max))
    84.3 (76.0 to 90.6) 0 (0 to 0) 0 (0 to 0) -
    Disease Control Rate (DCR) by Investigator
    DCR is the percentage (%) of subjects with a BOR of CR, PR, or SD, evaluated by CT or MRI scans every 28 days. Results are based on both BICR and on Investigator assessment. Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusions)
    Units: Percentage (%) with CR, PR, or SD
        median (full range (min-max))
    84.3 (76.0 to 90.6) 0 (0 to 0) 0 (0 to 0) -
    Overall Response Rate (ORR) as Assessed by the Investigator
    ORR is defined as the percentage (%) of subjects with a best overall response of CR or PR, evaluated by CT or MRI scans every 28 days. Due to early termination of the study, no formal efficacy analyses were performed for Cohorts 2 and 3. Overall Number of Participants Analyzed 108
    Units: Percentage (%)of subjects with CR or PR
        median (full range (min-max))
    32.4 (23.7 to 42.1) 0 (0 to 0) 0 (0 to 0) -
    Progression-Free Survival (PFS) by BICR
    PFS was calculated as the number of months from the first dose of study drug to the first documented progression or death due to any cause, whichever occurred earlier. Subjects without an assessment of progression or death were censored at the last adequate tumor assessment. For subjects who had an event after ≥2 missed visits, the subject was censored at the last adequate tumor assessment before the missing visit. Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusions)
    Units: Months
        median (full range (min-max))
    7.29 (5.59 to 7.56) 0 (0 to 0) 0 (0 to 0) -
    Progression-Free Survival (PFS) by Investigator
    PFS was calculated as the number of months from the first dose of study drug to the first documented progression or death due to any cause, whichever occurred earlier. Subjects without an assessment of progression or death were censored at the last adequate tumor assessment. For subjects who had an event after ≥2 missed visits, the subject was censored at the last adequate tumor assessment before the missing visit. Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusions)
    Units: months
        median (full range (min-max))
    6.74 (5.55 to 7.56) 0 (0 to 0) 0 (0 to 0) -
    Overall Survival (OS)
    OS was defined as the time (months) from the date of start of treatment to the date of death due to any cause. Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusions)
    Units: Months
        median (full range (min-max))
    11.86 (10.68 to 14.85) 0 (0 to 0) 0 (0 to 0) -
    Duration of Response (DOR) by investigator
    Number Analyzed: 35 DOR is defined as the time (months) from the initial response to the time of the event; defined as the first documented progression or death due to any cause, whichever was earlier. Note that results are based on a subgroup of subjects with confirmed responses (CR or PR) as assessed by BICR or by the Investigator. Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusions) Overall Number of Participants Analyzed 35
    Units: months
        median (full range (min-max))
    7.23 (5.16 to 9.00) 0 (0 to 0) 0 (0 to 0) -
    Duration of Response (DOR) by BICR
    Number analyzed : 25 DOR is defined as the time (months) from the initial response to the time of the event; defined as the first documented progression or death due to any cause, whichever was earlier. Note that results are based on a subgroup of subjects with confirmed responses (CR or PR) as assessed by BICR or by the Investigator.
    Units: Months
        median (full range (min-max))
    5.55 (3.78 to 7.66) 0 (0 to 0) 0 (0 to 0) -
    Response Onset by BICR
    Full Analysis Set (FAS), defined as all subjects in Cohort 1 who had received at least one dose of infigratinib. Conducted in a subgroup of subjects who were confirmed responders (CR or PR) as assessed by BICR (N = 25). Overall Number of Participants Analyzed 35
    Units: months
        median (full range (min-max))
    3.61 (1.38 to 7.36) 0 (0 to 0) 0 (0 to 0) -
    Growth Modulation Index (GMI) by BICR
    The GMI is defined as the ratio of PFS (months) during treatment with infigratinib relative to the time(months) to progression (TTP) during treatment with last prior line of therapy. Subjects served as their own control. Results are provided for both BICR and Investigator assessment. Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusions)
    Units: Ratio(PFS/TTP) in Months
        median (full range (min-max))
    1.22 (0.00 to 120) 0 (0 to 0) 0 (0 to 0) -
    Growth Modulation Index (GMI) by Investigator
    The GMI is defined as the ratio of PFS (months) during treatment with infigratinib relative to the time(months) to progression (TTP) during treatment with last prior line of therapy. Subjects served as their own control. Results are provided for both BICR and Investigator assessment. Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusions)
    Units: Ratio(PFS/TTP) in Months
        median (full range (min-max))
    1.24 (0.00 to 120) 0 (0 to 0) 0 (0 to 0) -
    Response Onset by Investigator
    Full Analysis Set (FAS), defined as all subjects in Cohort 1 who had received at least one dose of infigratinib. Conducted in a subgroup of subjects who were confirmed responders (CR or PR) as assessed by the Investigator (N = 35).
    Units: months
        median (full range (min-max))
    1.94 (1.38 to 18.76) 0 (0 to 0) 0 (0 to 0) -
    Retrospective Analysis of Post-second-line Antineoplastic Treatment Outcomes on ORR After 2nd-Line
    Post-hoc subgroup assessment of efficacy in those subjects who were receiving infigratinib as a third or later line of treatment. Investigator-assessed ORR was obtained from subjects' medical histories to provide a baseline evaluation of their response after historical second-line antineoplastic treatment prior to infigratinib treatment. Investigator-assessed ORR was then calculated in the same subjects after third- or later-line infigratinib therapy. Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (22 June 2022).
    Units: Percentage(%) of patients with CR or PR
        median (full range (min-max))
    0 (0.0 to 6.1) 0 (0 to 0) 0 (0 to 0) -
    Retrospective Analysis of Post-second-line Antineoplastic Treatment Outcomes on ORR - Third or Later
    Post-hoc subgroup assessment of efficacy in those subjects who were receiving infigratinib as a third or later line of treatment. Investigator-assessed ORR was obtained from subjects' medical histories to provide a baseline evaluation of their response after historical second-line antineoplastic treatment prior to infigratinib treatment. Investigator-assessed ORR was then calculated in the same subjects after third- or later-line infigratinib therapy. Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (22 June 2022).
    Units: Percentage(%) of patients with CR or PR
        median (full range (min-max))
    28.8 (17.8 to 42.1) 0 (0 to 0) 0 (0 to 0) -
    Retrospective Analysis of Post-second-line Antineoplastic Treatment Outcomes on PFS after 2nd line
    Post-hoc subgroup assessment of efficacy in those subjects who were receiving infigratinib as a third orlater line of treatment. Investigator-assessed PFS was obtained from subjects' medical histories to provide a baseline evaluationof their response after historical second-line antineoplastic treatment prior to infigratinib treatment.Investigator-assessed PFS was then calculated in the same subjects after third- or later-line infigratinibtherapy. Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusions) Analyzed:59
    Units: months
        median (full range (min-max))
    5.36 (3.25 to 8.15) 0 (0 to 0) 0 (0 to 0) -
    Retrospective Analysis of Post-second-line Antineoplastic Treatment Outcomes on PFS - Third or Later
    Post-hoc subgroup assessment of efficacy in those subjects who were receiving infigratinib as a third orlater line of treatment. Investigator-assessed PFS was obtained from subjects' medical histories to provide a baseline evaluationof their response after historical second-line antineoplastic treatment prior to infigratinib treatment.Investigator-assessed PFS was then calculated in the same subjects after third- or later-line infigratinibtherapy. Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusions) Analyzed : 59
    Units: months
        median (full range (min-max))
    6.93 (4.76 to 7.59) 0 (0 to 0) 0 (0 to 0) -
    Subject analysis sets

    Subject analysis set title
    Cohort 1
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Cohort 1 (FGFR2 fusions): Primary analysis population (N=108).

    Subject analysis set title
    Cohort 2
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Cohort 2 (Other FGFR alterations):N=25.

    Subject analysis set title
    Cohort 3
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Cohort 3 (FGFR2 fusions and prior FGFR inhibitor): N=10.

    Subject analysis sets values
    Cohort 1 Cohort 2 Cohort 3
    Number of subjects
    108
    25
    10
    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)
    82
    17
    8
        From 65-84 years
    26
    8
    2
        85 years and over
    0
    0
    0
    Age continuous
    Units:
        
    ( )
    ( )
    ( )
    Gender categorical
    Units: Subjects
        Female
    67
    12
    3
        Male
    41
    13
    7
    ECOG PS
    Measure Description: Functional status was assessed at baseline using the Eastern Cooperative Oncology Group Performance Scale (ECOG PS)
    Units: Subjects
        00
    45
    11
    3
        01
    62
    13
    7
        02
    1
    1
    0
    Primary site of cancer
    Primary site of cancer
    Units: Subjects
        Bile duct
    105
    24
    10
        Cholangiocarcinoma
    1
    1
    0
        Liver
    2
    0
    0
    Non-Liver MetastaticSite
    Units: Subjects
        No metastatic site
    5
    4
    0
        Had metastatic site
    102
    21
    10
        Missing
    1
    0
    0
    Histological Grade
    Units: Subjects
        Well differentiated
    9
    2
    0
        Moderately differentiated
    42
    14
    7
        Poorly differentiated
    33
    2
    2
        Undifferentiated
    1
    0
    0
        Unknown/missing
    22
    7
    1
        Not Applicable
    1
    0
    0
    Stage at Time of Study Entry
    The AJCC staging manual (7th edition) for intrahepaticcholangiocarcinoma was used for cancer staging at baseline, defined asfollows: Stage I: solitary tumor without vascular invasion. Stage II: solitary tumor withvascular invasion or multiple tumors with or without vascular invasion. Stage III: tumor perforating the visceral peritoneum or involving local hepaticstructure by direct invasion. Stage IV: tumor with periductal invasion, or any tumor with regional lymph node metastasis present, or any tumor with or without lymph node metastasis but metastasized to a distant site.
    Units: Subjects
        Stage II
    1
    3
    0
        Stage III
    0
    2
    0
        Stage IV
    107
    20
    10
    Best Overall Response (BOR) by Investigator
    BOR is defined as the best overall response a subject achieved during the study before any subsequent antineoplastic therapy. The endpoint is summarized for the rate of BOR of CR, PR, progressive disease(PD), and stable disease (SD), evaluated by CT or MRI scans every 28 days. Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusion) Overall Number of Participants Analyzed 108
    Units: Subjects
        Confirmed CR
    0
    0
    0
        Confirmed PR
    35
    0
    0
        Stable Disease
    56
    0
    0
        Progressive Disease
    11
    0
    0
        Not Done
    6
    25
    10
    Retrospective Analysis of Post-second-line Antineoplastic Treatment Outcomes on BOR - After 2nd line
    Post-hoc subgroup assessment of efficacy in those subjects who were receiving infigratinib as a third or later line of treatment. Note: The primary efficacy outcome measures were prespecified only for Cohort 1 Analyzed 59
    Units: Subjects
        Complete response
    0
    0
    0
        Partial response
    0
    0
    0
        Stable disease
    19
    0
    0
        Progressive disease
    22
    0
    0
        Unknown
    18
    0
    0
        Not done
    49
    25
    10
    Retrospective Analysis of Post-second-line Antineoplastic Treatment Outcomes on BOR - 3rd or later
    Post-hoc subgroup assessment of efficacy in those subjects who were receiving infigratinib as a third or later line of treatment. Note: The primary efficacy outcome measures were prespecified only for Cohort 1 Analyzed: 59
    Units: Subjects
        Complete response
    0
    0
    0
        Partial response
    17
    0
    0
        Stable disease
    31
    0
    0
        Progressive disease
    7
    0
    0
        Unknown
    0
    0
    0
        Not done
    53
    25
    10
    Overall Response Rate (ORR) as Assessed by Blinded Independent Central Imaging Review (BICR)
    ORR is defined as the percentage (%) of subjects with a best overall response of Complete Response(CR) or Partial Response (PR), as per Response Evaluation Criteria in Solid Tumors (RECIST), Version1.1, evaluated by computed tomography (CT) or magnetic resonance imaging (MRI) scans every 28 days. Due to early termination of the study, no formal efficacy analyses were performed for Cohorts 2 and 3. Overall Number of Participants Analyzed 108
    Units: Percentage (%)of subjects with CR or PR
        median (full range (min-max))
    23.1 (15.6 to 32.2)
    0 (0 to 0)
    0 (0 to 0)
    Disease Control Rate (DCR) by BICR
    DCR is the percentage (%) of subjects with a BOR of CR, PR, or SD, evaluated by CT or MRI scans every 28 days. Results are based on both BICR and on Investigator assessment. Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusions)
    Units: Percentage (%) with CR, PR, or SD
        median (full range (min-max))
    84.3 (76.0 to 90.6)
    0 (0 to 0)
    0 (0 to 0)
    Disease Control Rate (DCR) by Investigator
    DCR is the percentage (%) of subjects with a BOR of CR, PR, or SD, evaluated by CT or MRI scans every 28 days. Results are based on both BICR and on Investigator assessment. Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusions)
    Units: Percentage (%) with CR, PR, or SD
        median (full range (min-max))
    84.3 (76.0 to 90.6)
    0 (0 to 0)
    0 (0 to 0)
    Overall Response Rate (ORR) as Assessed by the Investigator
    ORR is defined as the percentage (%) of subjects with a best overall response of CR or PR, evaluated by CT or MRI scans every 28 days. Due to early termination of the study, no formal efficacy analyses were performed for Cohorts 2 and 3. Overall Number of Participants Analyzed 108
    Units: Percentage (%)of subjects with CR or PR
        median (full range (min-max))
    32.4 (23.7 to 42.1)
    0 (0 to 0)
    0 (0 to 0)
    Progression-Free Survival (PFS) by BICR
    PFS was calculated as the number of months from the first dose of study drug to the first documented progression or death due to any cause, whichever occurred earlier. Subjects without an assessment of progression or death were censored at the last adequate tumor assessment. For subjects who had an event after ≥2 missed visits, the subject was censored at the last adequate tumor assessment before the missing visit. Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusions)
    Units: Months
        median (full range (min-max))
    7.29 (5.59 to 7.56)
    0 (0 to 0)
    0 (0 to 0)
    Progression-Free Survival (PFS) by Investigator
    PFS was calculated as the number of months from the first dose of study drug to the first documented progression or death due to any cause, whichever occurred earlier. Subjects without an assessment of progression or death were censored at the last adequate tumor assessment. For subjects who had an event after ≥2 missed visits, the subject was censored at the last adequate tumor assessment before the missing visit. Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusions)
    Units: months
        median (full range (min-max))
    6.74 (5.55 to 7.56)
    0 (0 to 0)
    0 (0 to 0)
    Overall Survival (OS)
    OS was defined as the time (months) from the date of start of treatment to the date of death due to any cause. Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusions)
    Units: Months
        median (full range (min-max))
    11.86 (10.68 to 14.85)
    0 (0 to 0)
    0 (0 to 0)
    Duration of Response (DOR) by investigator
    Number Analyzed: 35 DOR is defined as the time (months) from the initial response to the time of the event; defined as the first documented progression or death due to any cause, whichever was earlier. Note that results are based on a subgroup of subjects with confirmed responses (CR or PR) as assessed by BICR or by the Investigator. Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusions) Overall Number of Participants Analyzed 35
    Units: months
        median (full range (min-max))
    7.23 (5.16 to 9.00)
    0 (0 to 0)
    0 (0 to 0)
    Duration of Response (DOR) by BICR
    Number analyzed : 25 DOR is defined as the time (months) from the initial response to the time of the event; defined as the first documented progression or death due to any cause, whichever was earlier. Note that results are based on a subgroup of subjects with confirmed responses (CR or PR) as assessed by BICR or by the Investigator.
    Units: Months
        median (full range (min-max))
    5.55 (3.78 to 7.66)
    0 (0 to 0)
    0 (0 to 0)
    Response Onset by BICR
    Full Analysis Set (FAS), defined as all subjects in Cohort 1 who had received at least one dose of infigratinib. Conducted in a subgroup of subjects who were confirmed responders (CR or PR) as assessed by BICR (N = 25). Overall Number of Participants Analyzed 35
    Units: months
        median (full range (min-max))
    3.61 (1.38 to 7.36)
    0 (0 to 0)
    0 (0 to 0)
    Growth Modulation Index (GMI) by BICR
    The GMI is defined as the ratio of PFS (months) during treatment with infigratinib relative to the time(months) to progression (TTP) during treatment with last prior line of therapy. Subjects served as their own control. Results are provided for both BICR and Investigator assessment. Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusions)
    Units: Ratio(PFS/TTP) in Months
        median (full range (min-max))
    1.22 (0.00 to 120)
    0 (0 to 0)
    0 (0 to 0)
    Growth Modulation Index (GMI) by Investigator
    The GMI is defined as the ratio of PFS (months) during treatment with infigratinib relative to the time(months) to progression (TTP) during treatment with last prior line of therapy. Subjects served as their own control. Results are provided for both BICR and Investigator assessment. Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusions)
    Units: Ratio(PFS/TTP) in Months
        median (full range (min-max))
    1.24 (0.00 to 120)
    0 (0 to 0)
    0 (0 to 0)
    Response Onset by Investigator
    Full Analysis Set (FAS), defined as all subjects in Cohort 1 who had received at least one dose of infigratinib. Conducted in a subgroup of subjects who were confirmed responders (CR or PR) as assessed by the Investigator (N = 35).
    Units: months
        median (full range (min-max))
    1.94 (1.38 to 18.76)
    0 (0 to 0)
    0 (0 to 0)
    Retrospective Analysis of Post-second-line Antineoplastic Treatment Outcomes on ORR After 2nd-Line
    Post-hoc subgroup assessment of efficacy in those subjects who were receiving infigratinib as a third or later line of treatment. Investigator-assessed ORR was obtained from subjects' medical histories to provide a baseline evaluation of their response after historical second-line antineoplastic treatment prior to infigratinib treatment. Investigator-assessed ORR was then calculated in the same subjects after third- or later-line infigratinib therapy. Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (22 June 2022).
    Units: Percentage(%) of patients with CR or PR
        median (full range (min-max))
    0 (0.0 to 6.1)
    0 (0 to 0)
    0 (0 to 0)
    Retrospective Analysis of Post-second-line Antineoplastic Treatment Outcomes on ORR - Third or Later
    Post-hoc subgroup assessment of efficacy in those subjects who were receiving infigratinib as a third or later line of treatment. Investigator-assessed ORR was obtained from subjects' medical histories to provide a baseline evaluation of their response after historical second-line antineoplastic treatment prior to infigratinib treatment. Investigator-assessed ORR was then calculated in the same subjects after third- or later-line infigratinib therapy. Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (22 June 2022).
    Units: Percentage(%) of patients with CR or PR
        median (full range (min-max))
    28.8 (17.8 to 42.1)
    0 (0 to 0)
    0 (0 to 0)
    Retrospective Analysis of Post-second-line Antineoplastic Treatment Outcomes on PFS after 2nd line
    Post-hoc subgroup assessment of efficacy in those subjects who were receiving infigratinib as a third orlater line of treatment. Investigator-assessed PFS was obtained from subjects' medical histories to provide a baseline evaluationof their response after historical second-line antineoplastic treatment prior to infigratinib treatment.Investigator-assessed PFS was then calculated in the same subjects after third- or later-line infigratinibtherapy. Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusions) Analyzed:59
    Units: months
        median (full range (min-max))
    5.36 (3.25 to 8.15)
    0 (0 to 0)
    0 (0 to 0)
    Retrospective Analysis of Post-second-line Antineoplastic Treatment Outcomes on PFS - Third or Later
    Post-hoc subgroup assessment of efficacy in those subjects who were receiving infigratinib as a third orlater line of treatment. Investigator-assessed PFS was obtained from subjects' medical histories to provide a baseline evaluationof their response after historical second-line antineoplastic treatment prior to infigratinib treatment.Investigator-assessed PFS was then calculated in the same subjects after third- or later-line infigratinibtherapy. Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusions) Analyzed : 59
    Units: months
        median (full range (min-max))
    6.93 (4.76 to 7.59)
    0 (0 to 0)
    0 (0 to 0)

    End points

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    End points reporting groups
    Reporting group title
    Cohort 1
    Reporting group description
    Subjects with FGFR2 fusions/rearrangements (N=108). These are the same 108 subjects as the main dataset presented in the interim CSR [X2204i] (“Interim Analysis Set 2 for Cohort 1”) and the primary CSR [X2204p] (“subjects with FGFR2 fusion/rearrangement in Cohort 1 FAS”); the only difference between reports was the length of follow-up (an additional 11 months). Note: No new efficacy analysis was done for the final CSR (aCSR), since these subs had completed their primary efficacy analysis (reported into he primary CSR)

    Reporting group title
    Cohort 2
    Reporting group description
    Cohort 2: Subjects with other FGFR alterations other than FGFR2 gene fusions or rearrangements (N=25). This cohort includes all 11 subjects enrolled to Cohort 2 and the 14 subjects with other FGFR alterations enrolled to Cohort 1 under the original protocol. Note: No efficacy analysis were performed since the study was terminated early.

    Reporting group title
    Cohort 3
    Reporting group description
    Cohort 3: Subjects with FGFR2 gene fusions/rearrangements who have received a prior FGFR inhibitor other than infigratinib (N=10). Note that Cohorts 2 and 3 were added at protocol amendment 4 to support exploratory objectives of the study and were not included in the analyses presented in the interim CSR [X2204i] or primary CSR [X2204p].

    Subject analysis set title
    Cohort 1
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Cohort 1 (FGFR2 fusions): Primary analysis population (N=108).

    Subject analysis set title
    Cohort 2
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Cohort 2 (Other FGFR alterations):N=25.

    Subject analysis set title
    Cohort 3
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Cohort 3 (FGFR2 fusions and prior FGFR inhibitor): N=10.

    Primary: Cohort 1

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    End point title
    Cohort 1 [1]
    End point description
    The primary endpoint for this study is overall response in Cohort 1 assessed according to blinded independent central review (BICR) using Response Evaluation Criteria in Solid Tumors
    End point type
    Primary
    End point timeframe
    TBC
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The primary endpoint for this study is overall response in Cohort 1 assessed according to blinded independent central review (BICR) using Response Evaluation Criteria in Solid Tumors
    End point values
    Cohort 1 Cohort 2 Cohort 3
    Number of subjects analysed
    108
    25
    10
    Units: overall response
    108
    25
    10
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first administration of infigratinib with follow-up of at least 10 months after initial exposure.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    21.0
    Reporting groups
    Reporting group title
    Cohort 1: FGFR2 Fusions
    Reporting group description
    -

    Reporting group title
    Cohort 3: FGFR2 Fusions and Prior FGFR Inhibitor
    Reporting group description
    -

    Reporting group title
    Cohort 2: Other FGFR Genetic Alterations
    Reporting group description
    -

    Serious adverse events
    Cohort 1: FGFR2 Fusions Cohort 3: FGFR2 Fusions and Prior FGFR Inhibitor Cohort 2: Other FGFR Genetic Alterations
    Total subjects affected by serious adverse events
         subjects affected / exposed
    35 / 108 (32.41%)
    2 / 10 (20.00%)
    11 / 25 (44.00%)
         number of deaths (all causes)
    93
    7
    19
         number of deaths resulting from adverse events
    2
    0
    1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Malignant melanoma
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Peripheral ischaemia
         subjects affected / exposed
    0 / 108 (0.00%)
    0 / 10 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Gait disturbance
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Asthenia
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    4 / 108 (3.70%)
    0 / 10 (0.00%)
    2 / 25 (8.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Pelvic pain
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Product issues
    Device occlusion
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Blood creatine increased
         subjects affected / exposed
    0 / 108 (0.00%)
    0 / 10 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Stress fracture
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    0 / 108 (0.00%)
    0 / 10 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Hepatic encephalopathy
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anemia
         subjects affected / exposed
    4 / 108 (3.70%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    2 / 108 (1.85%)
    0 / 10 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    2 / 108 (1.85%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    2 / 108 (1.85%)
    1 / 10 (10.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    2 / 108 (1.85%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer haemorrhage
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Noninfective sialoadenitis
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 10 (10.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intestinal ischaemia
         subjects affected / exposed
    0 / 108 (0.00%)
    0 / 10 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 10 (10.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 10 (10.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct obstruction
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic function abnormal
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholangitis
         subjects affected / exposed
    2 / 108 (1.85%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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 / 108 (0.93%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Urinary retention
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute kidney injury
         subjects affected / exposed
    2 / 108 (1.85%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arthralgia
         subjects affected / exposed
    0 / 108 (0.00%)
    0 / 10 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    0 / 108 (0.00%)
    0 / 10 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bone pain
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myalgia
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    0 / 108 (0.00%)
    0 / 10 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Clostridium difficile colitis
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Biliary abscess
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    2 / 108 (1.85%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Febrile infection
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    2 / 108 (1.85%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 108 (0.00%)
    0 / 10 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intervertebral discitis
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peritonitis bacterial
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    3 / 108 (2.78%)
    0 / 10 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Calciphylaxis
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    4 / 108 (3.70%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperphosphataemia
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypophosphataemia
         subjects affected / exposed
    2 / 108 (1.85%)
    1 / 10 (10.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 1%
    Non-serious adverse events
    Cohort 1: FGFR2 Fusions Cohort 3: FGFR2 Fusions and Prior FGFR Inhibitor Cohort 2: Other FGFR Genetic Alterations
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    107 / 108 (99.07%)
    10 / 10 (100.00%)
    25 / 25 (100.00%)
    Vascular disorders
    Hypotension
         subjects affected / exposed
    0 / 108 (0.00%)
    0 / 10 (0.00%)
    3 / 25 (12.00%)
         occurrences all number
    0
    0
    0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    17 / 108 (15.74%)
    1 / 10 (10.00%)
    3 / 25 (12.00%)
         occurrences all number
    0
    0
    0
    Asthenia
         subjects affected / exposed
    6 / 108 (5.56%)
    0 / 10 (0.00%)
    1 / 25 (4.00%)
         occurrences all number
    0
    0
    0
    Chills
         subjects affected / exposed
    8 / 108 (7.41%)
    0 / 10 (0.00%)
    1 / 25 (4.00%)
         occurrences all number
    0
    0
    0
    Fatigue
         subjects affected / exposed
    44 / 108 (40.74%)
    3 / 10 (30.00%)
    10 / 25 (40.00%)
         occurrences all number
    0
    0
    0
    Non-cardiac chest pain
         subjects affected / exposed
    6 / 108 (5.56%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences all number
    0
    0
    0
    Oedema peripheral
         subjects affected / exposed
    15 / 108 (13.89%)
    1 / 10 (10.00%)
    3 / 25 (12.00%)
         occurrences all number
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    14 / 108 (12.96%)
    1 / 10 (10.00%)
    4 / 25 (16.00%)
         occurrences all number
    0
    0
    0
    Dyspnoea
         subjects affected / exposed
    10 / 108 (9.26%)
    1 / 10 (10.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    0
    0
    Epistaxis
         subjects affected / exposed
    19 / 108 (17.59%)
    6 / 10 (60.00%)
    5 / 25 (20.00%)
         occurrences all number
    0
    0
    0
    Hiccups
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    3 / 25 (12.00%)
         occurrences all number
    0
    0
    0
    Oropharyngeal pain
         subjects affected / exposed
    9 / 108 (8.33%)
    0 / 10 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    0
    0
    Rhinorrhoea
         subjects affected / exposed
    0 / 108 (0.00%)
    0 / 10 (0.00%)
    3 / 25 (12.00%)
         occurrences all number
    0
    0
    0
    Wheezing
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 10 (10.00%)
    0 / 25 (0.00%)
         occurrences all number
    0
    0
    0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    14 / 108 (12.96%)
    2 / 10 (20.00%)
    0 / 25 (0.00%)
         occurrences all number
    0
    0
    0
    Investigations
    Weight decreased
         subjects affected / exposed
    17 / 108 (15.74%)
    0 / 10 (0.00%)
    5 / 25 (20.00%)
         occurrences all number
    0
    0
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    18 / 108 (16.67%)
    0 / 10 (0.00%)
    4 / 25 (16.00%)
         occurrences all number
    0
    0
    0
    Amylase increased
         subjects affected / exposed
    7 / 108 (6.48%)
    0 / 10 (0.00%)
    1 / 25 (4.00%)
         occurrences all number
    0
    0
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    25 / 108 (23.15%)
    0 / 10 (0.00%)
    7 / 25 (28.00%)
         occurrences all number
    0
    0
    0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    17 / 108 (15.74%)
    0 / 10 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    0
    0
    Blood bilirubin increased
         subjects affected / exposed
    9 / 108 (8.33%)
    1 / 10 (10.00%)
    0 / 25 (0.00%)
         occurrences all number
    0
    0
    0
    Blood creatinine increased
         subjects affected / exposed
    27 / 108 (25.00%)
    1 / 10 (10.00%)
    8 / 25 (32.00%)
         occurrences all number
    0
    0
    0
    Creatinine renal clearance decreased
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 10 (10.00%)
    0 / 25 (0.00%)
         occurrences all number
    0
    0
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 10 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    0
    0
    Lipase increased
         subjects affected / exposed
    13 / 108 (12.04%)
    0 / 10 (0.00%)
    4 / 25 (16.00%)
         occurrences all number
    0
    0
    0
    Platelet count decreased
         subjects affected / exposed
    0 / 108 (0.00%)
    0 / 10 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    0
    0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 10 (10.00%)
    1 / 25 (4.00%)
         occurrences all number
    0
    0
    0
    Post-traumatic pain
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 10 (10.00%)
    0 / 25 (0.00%)
         occurrences all number
    0
    0
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    10 / 108 (9.26%)
    0 / 10 (0.00%)
    3 / 25 (12.00%)
         occurrences all number
    0
    0
    0
    Dysgeusia
         subjects affected / exposed
    34 / 108 (31.48%)
    0 / 10 (0.00%)
    6 / 25 (24.00%)
         occurrences all number
    0
    0
    0
    Headache
         subjects affected / exposed
    19 / 108 (17.59%)
    3 / 10 (30.00%)
    4 / 25 (16.00%)
         occurrences all number
    0
    0
    0
    Memory impairment
         subjects affected / exposed
    6 / 108 (5.56%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences all number
    0
    0
    0
    Peripheral motor neuropathy
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 10 (10.00%)
    0 / 25 (0.00%)
         occurrences all number
    0
    0
    0
    Peripheral sensory neuropathy
         subjects affected / exposed
    6 / 108 (5.56%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences all number
    0
    0
    0
    Blood and lymphatic system disorders
    Thrombocytopenia
         subjects affected / exposed
    9 / 108 (8.33%)
    0 / 10 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    0
    0
    Lymphopenia
         subjects affected / exposed
    7 / 108 (6.48%)
    0 / 10 (0.00%)
    1 / 25 (4.00%)
         occurrences all number
    0
    0
    0
    Neutropenia
         subjects affected / exposed
    7 / 108 (6.48%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences all number
    0
    0
    0
    Anaemia
         subjects affected / exposed
    20 / 108 (18.52%)
    0 / 10 (0.00%)
    5 / 25 (20.00%)
         occurrences all number
    0
    0
    0
    Eye disorders
    Blepharitis
         subjects affected / exposed
    12 / 108 (11.11%)
    0 / 10 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    0
    0
    Cataract
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 10 (10.00%)
    1 / 25 (4.00%)
         occurrences all number
    0
    0
    0
    Cataract nuclear
         subjects affected / exposed
    8 / 108 (7.41%)
    1 / 10 (10.00%)
    0 / 25 (0.00%)
         occurrences all number
    0
    0
    0
    Chorioretinopathy
         subjects affected / exposed
    10 / 108 (9.26%)
    1 / 10 (10.00%)
    0 / 25 (0.00%)
         occurrences all number
    0
    0
    0
    Dry eye
         subjects affected / exposed
    39 / 108 (36.11%)
    4 / 10 (40.00%)
    3 / 25 (12.00%)
         occurrences all number
    0
    0
    0
    Keratopathy
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 10 (10.00%)
    0 / 25 (0.00%)
         occurrences all number
    0
    0
    0
    Growth of eyelashes
         subjects affected / exposed
    7 / 108 (6.48%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences all number
    0
    0
    0
    Keratitis
         subjects affected / exposed
    7 / 108 (6.48%)
    0 / 10 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    0
    0
    Eye pain
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 10 (10.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    0
    0
    Lacrimation increased
         subjects affected / exposed
    13 / 108 (12.04%)
    0 / 10 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    0
    0
    Ocular hyperaemia
         subjects affected / exposed
    6 / 108 (5.56%)
    0 / 10 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    0
    0
    Punctate keratitis
         subjects affected / exposed
    10 / 108 (9.26%)
    0 / 10 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    0
    0
    Retinal drusen
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 10 (10.00%)
    0 / 25 (0.00%)
         occurrences all number
    0
    0
    0
    Subretinal fluid
         subjects affected / exposed
    6 / 108 (5.56%)
    0 / 10 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    0
    0
    Trichomegaly
         subjects affected / exposed
    0 / 108 (0.00%)
    0 / 10 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    0
    0
    Vision blurred
         subjects affected / exposed
    23 / 108 (21.30%)
    1 / 10 (10.00%)
    4 / 25 (16.00%)
         occurrences all number
    0
    0
    0
    Visual acuity reduced
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 10 (10.00%)
    1 / 25 (4.00%)
         occurrences all number
    0
    0
    0
    Vitreous detachment
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 10 (10.00%)
    0 / 25 (0.00%)
         occurrences all number
    0
    0
    0
    Trichiasis
         subjects affected / exposed
    13 / 108 (12.04%)
    0 / 10 (0.00%)
    4 / 25 (16.00%)
         occurrences all number
    0
    0
    0
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    0 / 108 (0.00%)
    0 / 10 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    0
    0
    Abdominal distension
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 10 (10.00%)
    0 / 25 (0.00%)
         occurrences all number
    0
    0
    0
    Abdominal pain
         subjects affected / exposed
    19 / 108 (17.59%)
    1 / 10 (10.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    0
    0
    Abdominal pain lower
         subjects affected / exposed
    0 / 108 (0.00%)
    0 / 10 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    0
    0
    Abdominal pain upper
         subjects affected / exposed
    16 / 108 (14.81%)
    0 / 10 (0.00%)
    4 / 25 (16.00%)
         occurrences all number
    0
    0
    0
    Ascites
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 10 (10.00%)
    0 / 25 (0.00%)
         occurrences all number
    0
    0
    0
    Constipation
         subjects affected / exposed
    34 / 108 (31.48%)
    3 / 10 (30.00%)
    11 / 25 (44.00%)
         occurrences all number
    0
    0
    0
    Nausea
         subjects affected / exposed
    21 / 108 (19.44%)
    3 / 10 (30.00%)
    10 / 25 (40.00%)
         occurrences all number
    0
    0
    0
    Dry mouth
         subjects affected / exposed
    28 / 108 (25.93%)
    1 / 10 (10.00%)
    7 / 25 (28.00%)
         occurrences all number
    0
    0
    0
    Dyspepsia
         subjects affected / exposed
    20 / 108 (18.52%)
    0 / 10 (0.00%)
    3 / 25 (12.00%)
         occurrences all number
    0
    0
    0
    Dysphagia
         subjects affected / exposed
    7 / 108 (6.48%)
    0 / 10 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    0
    0
    Food poisoning
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 10 (10.00%)
    0 / 25 (0.00%)
         occurrences all number
    0
    0
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    6 / 108 (5.56%)
    1 / 10 (10.00%)
    1 / 25 (4.00%)
         occurrences all number
    0
    0
    0
    Diarrhoea
         subjects affected / exposed
    27 / 108 (25.00%)
    3 / 10 (30.00%)
    8 / 25 (32.00%)
         occurrences all number
    0
    0
    0
    Oral dysaesthesia
         subjects affected / exposed
    0 / 108 (0.00%)
    0 / 10 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    0
    0
    Retching
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 10 (10.00%)
    0 / 25 (0.00%)
         occurrences all number
    0
    0
    0
    Stomatitis
         subjects affected / exposed
    59 / 108 (54.63%)
    7 / 10 (70.00%)
    13 / 25 (52.00%)
         occurrences all number
    0
    0
    0
    Vomiting
         subjects affected / exposed
    25 / 108 (23.15%)
    3 / 10 (30.00%)
    5 / 25 (20.00%)
         occurrences all number
    0
    0
    0
    Oral pain
         subjects affected / exposed
    6 / 108 (5.56%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences all number
    0
    0
    0
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    8 / 108 (7.41%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences all number
    0
    0
    0
    Pruritus
         subjects affected / exposed
    7 / 108 (6.48%)
    2 / 10 (20.00%)
    0 / 25 (0.00%)
         occurrences all number
    0
    0
    0
    Alopecia
         subjects affected / exposed
    43 / 108 (39.81%)
    1 / 10 (10.00%)
    9 / 25 (36.00%)
         occurrences all number
    0
    0
    0
    Dry skin
         subjects affected / exposed
    26 / 108 (24.07%)
    3 / 10 (30.00%)
    4 / 25 (16.00%)
         occurrences all number
    0
    0
    0
    Erythema
         subjects affected / exposed
    0 / 108 (0.00%)
    0 / 10 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    0
    0
    Hyperkeratosis
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 10 (10.00%)
    1 / 25 (4.00%)
         occurrences all number
    0
    0
    0
    Nail discolouration
         subjects affected / exposed
    20 / 108 (18.52%)
    2 / 10 (20.00%)
    4 / 25 (16.00%)
         occurrences all number
    0
    0
    0
    Nail disorder
         subjects affected / exposed
    17 / 108 (15.74%)
    0 / 10 (0.00%)
    3 / 25 (12.00%)
         occurrences all number
    0
    0
    0
    Nail ridging
         subjects affected / exposed
    8 / 108 (7.41%)
    1 / 10 (10.00%)
    0 / 25 (0.00%)
         occurrences all number
    0
    0
    0
    Onychalgia
         subjects affected / exposed
    14 / 108 (12.96%)
    0 / 10 (0.00%)
    1 / 25 (4.00%)
         occurrences all number
    0
    0
    0
    Onycholysis
         subjects affected / exposed
    14 / 108 (12.96%)
    2 / 10 (20.00%)
    4 / 25 (16.00%)
         occurrences all number
    0
    0
    0
    Onychomadesis
         subjects affected / exposed
    19 / 108 (17.59%)
    0 / 10 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    0
    0
    Pain of skin
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 10 (10.00%)
    0 / 25 (0.00%)
         occurrences all number
    0
    0
    0
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    37 / 108 (34.26%)
    5 / 10 (50.00%)
    6 / 25 (24.00%)
         occurrences all number
    0
    0
    0
    Skin exfoliation
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 10 (10.00%)
    0 / 25 (0.00%)
         occurrences all number
    0
    0
    0
    Rash maculo-papular
         subjects affected / exposed
    6 / 108 (5.56%)
    0 / 10 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    0
    0
    Renal and urinary disorders
    Chromaturia
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 10 (10.00%)
    0 / 25 (0.00%)
         occurrences all number
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    35 / 108 (32.41%)
    1 / 10 (10.00%)
    4 / 25 (16.00%)
         occurrences all number
    0
    0
    0
    Coccydynia
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 10 (10.00%)
    1 / 25 (4.00%)
         occurrences all number
    0
    0
    0
    Flank pain
         subjects affected / exposed
    7 / 108 (6.48%)
    2 / 10 (20.00%)
    0 / 25 (0.00%)
         occurrences all number
    0
    0
    0
    Muscular weakness
         subjects affected / exposed
    7 / 108 (6.48%)
    0 / 10 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    0
    0
    Back pain
         subjects affected / exposed
    16 / 108 (14.81%)
    1 / 10 (10.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    0
    0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 108 (0.00%)
    0 / 10 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    0
    0
    Myalgia
         subjects affected / exposed
    14 / 108 (12.96%)
    0 / 10 (0.00%)
    4 / 25 (16.00%)
         occurrences all number
    0
    0
    0
    Pain in extremity
         subjects affected / exposed
    17 / 108 (15.74%)
    1 / 10 (10.00%)
    5 / 25 (20.00%)
         occurrences all number
    0
    0
    0
    Pain in jaw
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 10 (10.00%)
    0 / 25 (0.00%)
         occurrences all number
    0
    0
    0
    Infections and infestations
    Enterocolitis infectious
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 10 (10.00%)
    0 / 25 (0.00%)
         occurrences all number
    0
    0
    0
    Infection
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 10 (10.00%)
    0 / 25 (0.00%)
         occurrences all number
    0
    0
    0
    Paronychia
         subjects affected / exposed
    11 / 108 (10.19%)
    0 / 10 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    0
    0
    Urinary tract infection
         subjects affected / exposed
    10 / 108 (9.26%)
    1 / 10 (10.00%)
    3 / 25 (12.00%)
         occurrences all number
    0
    0
    0
    Vulvovaginal candidiasis
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 10 (10.00%)
    0 / 25 (0.00%)
         occurrences all number
    0
    0
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    26 / 108 (24.07%)
    3 / 10 (30.00%)
    7 / 25 (28.00%)
         occurrences all number
    0
    0
    0
    Dehydration
         subjects affected / exposed
    7 / 108 (6.48%)
    0 / 10 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    0
    0
    Hypophosphataemia
         subjects affected / exposed
    25 / 108 (23.15%)
    2 / 10 (20.00%)
    5 / 25 (20.00%)
         occurrences all number
    0
    0
    0
    Hypercalcaemia
         subjects affected / exposed
    29 / 108 (26.85%)
    1 / 10 (10.00%)
    5 / 25 (20.00%)
         occurrences all number
    0
    0
    0
    Hyperkalaemia
         subjects affected / exposed
    9 / 108 (8.33%)
    0 / 10 (0.00%)
    1 / 25 (4.00%)
         occurrences all number
    0
    0
    0
    Hyperphosphataemia
         subjects affected / exposed
    83 / 108 (76.85%)
    7 / 10 (70.00%)
    23 / 25 (92.00%)
         occurrences all number
    0
    0
    0
    Hypertriglyceridaemia
         subjects affected / exposed
    7 / 108 (6.48%)
    0 / 10 (0.00%)
    1 / 25 (4.00%)
         occurrences all number
    0
    0
    0
    Hyperuricaemia
         subjects affected / exposed
    8 / 108 (7.41%)
    0 / 10 (0.00%)
    0 / 25 (0.00%)
         occurrences all number
    0
    0
    0
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 108 (0.00%)
    0 / 10 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    0
    0
    Hypokalaemia
         subjects affected / exposed
    8 / 108 (7.41%)
    0 / 10 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    0
    0
    Hypomagnesaemia
         subjects affected / exposed
    9 / 108 (8.33%)
    0 / 10 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    0
    0
    Hyponatraemia
         subjects affected / exposed
    14 / 108 (12.96%)
    1 / 10 (10.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    0
    0

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    15 Jan 2020
    Protocol version 6 (protocol amendment 5) dated 15 January 2020 The primary purpose of this amendment was to revise the protocol based on updates to standards for safety and study conduct for BGJ398 and to add a second interim analysis for Cohort 1 when all the patients who received BGJ398 at the time of the first formal interim analysis have at least 10 months follow-up after their initial exposure to BGJ398.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

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