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    Clinical Trial Results:
    An international, multicenter, Phase 1b/2 study of rogaratinib (BAY 1163877) in combination with atezolizumab as first-line treatment in cisplatin-ineligible patients with FGFR-positive locally advanced or metastatic urothelial carcinoma

    Summary
    EudraCT number
    		 2017-001483-38
    Trial protocol
    		 DE   ES   FR   AT  
    Global end of trial date
    10 Jul 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    07 Mar 2025
    First version publication date
    07 Mar 2025
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    BAY1163877/19131
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03473756
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Bayer AG
    Sponsor organisation address
    Kaiser-Wilhelm-Allee, Leverkusen, Germany, 51368
    Public contact
    Bayer Clinical Trials Contact, Bayer AG, clinical-trials-contact@bayer.com
    Scientific contact
    Bayer Clinical Trials Contact, Bayer AG, clinical-trials-contact@bayer.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
    07 Aug 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    10 Jul 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    • To determine the safety and tolerability of rogaratinib in combination with atezolizumab in patients with FGFR-positive locally advanced or metastatic urothelial carcinoma • To determine the recommended Phase 2 dose (RP2D) of rogaratinib in combination with atezolizumab in this patient population.
    Protection of trial subjects
    The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with ethical principles that have their origin in the Declaration of Helsinki and the International Council for Harmonization guideline E6: Good Clinical Practice. Before entering the study, the informed consent was read by and explained to all the subjects. Participating subjects signed informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    15 May 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 9
    Country: Number of subjects enrolled
    Austria: 3
    Country: Number of subjects enrolled
    France: 4
    Country: Number of subjects enrolled
    Germany: 3
    Country: Number of subjects enrolled
    Italy: 6
    Country: Number of subjects enrolled
    Japan: 2
    Country: Number of subjects enrolled
    Korea, Republic of: 6
    Country: Number of subjects enrolled
    United States: 4
    Worldwide total number of subjects
    37
    EEA total number of subjects
    25
    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)
    4
    From 65 to 84 years
    32
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    		 The study was conducted at 30 study centers in 8 countries (4 in Austria, 3 in France, 3 in Germany, 5 in Italy, 4 in Japan, 3 in South Korea, 4 in Spain, and 4 in the US) between 15 May 2018 (first informed consent) and 10 July 2024 (last participant last visit).

    Pre-assignment
    Screening details
    		 A total of 54 FGFR mRNA-positive subjects (35.3%) successfully completed the prescreening. Of these, 37 subjects (68.5%) completed the screening and were assigned to treatment and 31.5% prematurely discontinued the screening: 29.6% due to screening failure and 1.9% (1 subject) due to withdrawal by subject.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Rogaratinib 800 mg BID + Atezolizumab
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Rogaratinib
    Investigational medicinal product code
    Other name
    BAY 1163877 / rogaratinib / pan FGFR inhibitor
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Starting dose level of rogaratinib was 800 mg twice daily (BID), in continuous 21-day cycles. Suggested by safety findings, the dose was lowered to rogaratinib 600 mg BID when given in combination with 1200 mg atezolizumab every 21 days.

    Arm title
    		 Rogaratinib 600 mg BID + Atezolizumab
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Rogaratinib
    Investigational medicinal product code
    Other name
    BAY 1163877 / rogaratinib / pan FGFR inhibitor
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Starting dose level of rogaratinib was 800 mg twice daily (BID), in continuous 21-day cycles. Suggested by safety findings, the dose was lowered to rogaratinib 600 mg BID when given in combination with 1200 mg atezolizumab every 21 days.

    Number of subjects in period 1
    		Rogaratinib 800 mg BID + Atezolizumab Rogaratinib 600 mg BID + Atezolizumab
    Started
    11
    26
    Completed
    1
    0
    Not completed
    10
    26
         Consent withdrawn by subject
    1
    4
         Physician decision
    -
    2
         Adverse event, non-fatal
    6
    7
         End of study treatment
    -
    2
         Lost to follow-up
    -
    1
         Lack of efficacy
    3
    10

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Rogaratinib 800 mg BID + Atezolizumab
    Reporting group description
    		 -

    Reporting group title
    Rogaratinib 600 mg BID + Atezolizumab
    Reporting group description
    		 -

    Reporting group values
    		 Rogaratinib 800 mg BID + Atezolizumab Rogaratinib 600 mg BID + Atezolizumab Total
    Number of subjects
    		 11 26 37
    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)
    		 2 2 4
        From 65-84 years
    		 9 23 32
        85 years and over
    		 0 1 1
    Gender categorical
    Units: Subjects
        Female
    		 2 3 5
        Male
    		 9 23 32
    Subject analysis sets

    Subject analysis set title
    All participants assigned to treatment
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All participants, who successfully passed screening and were assigned to study treatment and received at least one dose of study treatment:

    Subject analysis sets values
    		 All participants assigned to treatment
    Number of subjects
    37
    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)
    4
        From 65-84 years
    32
        85 years and over
    1
    Age continuous
    Units:
        
    ( )
    Gender categorical
    Units: Subjects
        Female
    5
        Male
    32

    End points

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    End points reporting groups
    Reporting group title
    Rogaratinib 800 mg BID + Atezolizumab
    Reporting group description
    		 -

    Reporting group title
    Rogaratinib 600 mg BID + Atezolizumab
    Reporting group description
    		 -

    Subject analysis set title
    All participants assigned to treatment
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All participants, who successfully passed screening and were assigned to study treatment and received at least one dose of study treatment:

    Primary: Number of participants with Dose-limiting toxicities(DLTs)

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    End point title
    		 Number of participants with Dose-limiting toxicities(DLTs) [1]
    End point description
    End point type
    Primary
    End point timeframe
    Up to 21 days
    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: Due to the limited number of patients, statistical analyses included in this study focused on descriptive statistics only. Comparisons between Rogaratinib 800 mg and Rogaratinib 600 mg are not considered meaningful
    End point values
    		 Rogaratinib 800 mg BID + Atezolizumab Rogaratinib 600 mg BID + Atezolizumab
    Number of subjects analysed
    11
    26
    Units: participants
    1
    4
    No statistical analyses for this end point

    Primary: Number of participants with treatment-emergent adverse events (TEAEs)

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    End point title
    		 Number of participants with treatment-emergent adverse events (TEAEs) [2]
    End point description
    End point type
    Primary
    End point timeframe
    Up to 30 days after the last dose of rogaratinib or 90 days after the last atezolizumab administration, whichever comes later
    Notes
    [2] - 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: Due to the limited number of patients, statistical analyses included in this study focused on descriptive statistics only. Comparisons between Rogaratinib 800 mg and Rogaratinib 600 mg are not considered meaningful
    End point values
    		 Rogaratinib 800 mg BID + Atezolizumab Rogaratinib 600 mg BID + Atezolizumab
    Number of subjects analysed
    11
    26
    Units: participants
    11
    26
    No statistical analyses for this end point

    Primary: Number of participants with drug-related TEAEs

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    End point title
    		 Number of participants with drug-related TEAEs [3]
    End point description
    End point type
    Primary
    End point timeframe
    Up to 30 days after the last dose of rogaratinib or 90 days after the last atezolizumab administration, whichever comes later
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the limited number of patients, statistical analyses included in this study focused on descriptive statistics only. Comparisons between Rogaratinib 800 mg and Rogaratinib 600 mg are not considered meaningful
    End point values
    		 Rogaratinib 800 mg BID + Atezolizumab Rogaratinib 600 mg BID + Atezolizumab
    Number of subjects analysed
    11
    26
    Units: participants
    11
    26
    No statistical analyses for this end point

    Primary: Number of participants with treatment-emergent serious adverse events(TESAEs)

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    End point title
    		 Number of participants with treatment-emergent serious adverse events(TESAEs) [4]
    End point description
    End point type
    Primary
    End point timeframe
    Up to 30 days after the last dose of rogaratinib or 90 days after the last atezolizumab administration, whichever comes later
    Notes
    [4] - 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: Due to the limited number of patients, statistical analyses included in this study focused on descriptive statistics only. Comparisons between Rogaratinib 800 mg and Rogaratinib 600 mg are not considered meaningful
    End point values
    		 Rogaratinib 800 mg BID + Atezolizumab Rogaratinib 600 mg BID + Atezolizumab
    Number of subjects analysed
    11
    26
    Units: participants
    8
    14
    No statistical analyses for this end point

    Secondary: Objective Response Rate(ORR)

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    End point title
    		 Objective Response Rate(ORR)
    End point description
    Objective response rate (ORR) was defined as the percentage of patients with complete response (CR) or partial response (PR). Patients for whom best overall tumor response was not CR or PR, as well as patients without any post-baseline tumor assessment were considered non-responders. For all patients, the best overall tumor response was determined locally by investigators using the RECIST (Response Evaluation Criteria In Solid Tumors) criteria.
    End point type
    Secondary
    End point timeframe
    Up to 5 months
    End point values
    		 Rogaratinib 800 mg BID + Atezolizumab Rogaratinib 600 mg BID + Atezolizumab
    Number of subjects analysed
    11
    26
    Units: participants
        complete response
    1
    4
        partial response
    1
    10
        no response
    9
    12
    No statistical analyses for this end point

    Secondary: Maximal plasma concentration (Cmax) of rogaratinib

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    End point title
    		 Maximal plasma concentration (Cmax) of rogaratinib
    End point description
    End point type
    Secondary
    End point timeframe
    At cycle 1 Day 1
    End point values
    		 Rogaratinib 800 mg BID + Atezolizumab Rogaratinib 600 mg BID + Atezolizumab
    Number of subjects analysed
    11
    25 [5]
    Units: µg/l
        geometric mean (standard deviation)
    13207.846 ( 1.379 )
    10372.864 ( 1.404 )
    Notes
    [5] - Pharmacokinetic analysis set
    No statistical analyses for this end point

    Secondary: Area under the rogaratinib concentration versus time curve (AUC)

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    End point title
    		 Area under the rogaratinib concentration versus time curve (AUC)
    End point description
    End point type
    Secondary
    End point timeframe
    At cycle 1 Day 1, 0-t(last)
    End point values
    		 Rogaratinib 800 mg BID + Atezolizumab Rogaratinib 600 mg BID + Atezolizumab
    Number of subjects analysed
    11
    25 [6]
    Units: µg*h/l
        geometric mean (standard deviation)
    59187.389 ( 1.513 )
    45094.877 ( 1.463 )
    Notes
    [6] - pharmacokinetic analysis set
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Treatment-emergent adverse events (TEAEs) were defined as any event arising or worsening after the start of study drug administration until 30 days after the last rogaratinib intake or 90 days after the last atezolizumab administration
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    27.0
    Reporting groups
    Reporting group title
    Rogaratinib 800 mg BID + Atezolizumab
    Reporting group description
    		 Subjects received Rogaratinib 800 mg twice daily (b.i.d.) continuously twice daily on all 21 days in each cycle and 1200 mg Atezolizumab through intravenous (i.v.) infusion on Day 1 of each 21-day cycle.

    Reporting group title
    Rogaratinib 600 mg BID + Atezolizumab
    Reporting group description
    		 Subjects received Rogaratinib 600 mg twice daily (b.i.d.) continuously twice daily on all 21 days in each cycle and 1200 mg Atezolizumab through intravenous (i.v.) infusion on Day 1 of each 21-day cycle.

    Serious adverse events
    		 Rogaratinib 800 mg BID + Atezolizumab Rogaratinib 600 mg BID + Atezolizumab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    8 / 11 (72.73%)
    14 / 26 (53.85%)
         number of deaths (all causes)
    9
    11
         number of deaths resulting from adverse events
    1
    3
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Chronic lymphocytic leukaemia
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tumour haemorrhage
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Circulatory collapse
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Renal cyst aspiration
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal function test abnormal
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Vascular pseudoaneurysm
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haematoma
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Craniocerebral injury
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiac disorders
    Angina unstable
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Nervous system disorders
    Syncope
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea haemorrhagic
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal vascular malformation haemorrhagic
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatitis
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatotoxicity
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Angioedema
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal impairment
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pyelonephritis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Rogaratinib 800 mg BID + Atezolizumab Rogaratinib 600 mg BID + Atezolizumab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    11 / 11 (100.00%)
    26 / 26 (100.00%)
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 26 (3.85%)
         occurrences all number
    1
    2
    Hypotension
         subjects affected / exposed
    0 / 11 (0.00%)
    3 / 26 (11.54%)
         occurrences all number
    0
    3
    Erythromelalgia
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Hypertension
         subjects affected / exposed
    0 / 11 (0.00%)
    4 / 26 (15.38%)
         occurrences all number
    0
    4
    Embolism
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Peripheral arterial occlusive disease
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    2
    Surgical and medical procedures
    Astringent therapy
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    4
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    4 / 11 (36.36%)
    7 / 26 (26.92%)
         occurrences all number
    13
    11
    Fatigue
         subjects affected / exposed
    4 / 11 (36.36%)
    11 / 26 (42.31%)
         occurrences all number
    6
    26
    Chills
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Chest pain
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Hyperpyrexia
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    4
    Influenza like illness
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Injection site reaction
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Mucosal inflammation
         subjects affected / exposed
    2 / 11 (18.18%)
    2 / 26 (7.69%)
         occurrences all number
    3
    4
    Pain
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Oedema peripheral
         subjects affected / exposed
    0 / 11 (0.00%)
    5 / 26 (19.23%)
         occurrences all number
    0
    5
    Oedema
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Pyrexia
         subjects affected / exposed
    4 / 11 (36.36%)
    7 / 26 (26.92%)
         occurrences all number
    13
    10
    Early satiety
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Secretion discharge
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    General physical health deterioration
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Reproductive system and breast disorders
    Pelvic pain
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Erectile dysfunction
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Breast pain
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Cough
         subjects affected / exposed
    0 / 11 (0.00%)
    3 / 26 (11.54%)
         occurrences all number
    0
    4
    Dysphonia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Dyspnoea
         subjects affected / exposed
    0 / 11 (0.00%)
    3 / 26 (11.54%)
         occurrences all number
    0
    3
    Lower respiratory tract congestion
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    3
    Pneumothorax
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Epistaxis
         subjects affected / exposed
    0 / 11 (0.00%)
    3 / 26 (11.54%)
         occurrences all number
    0
    4
    Hiccups
         subjects affected / exposed
    0 / 11 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    2
    Nasal inflammation
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Pleural effusion
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    2
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Personality change
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Insomnia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Depression
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Product issues
    Thrombosis in device
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 11 (9.09%)
    8 / 26 (30.77%)
         occurrences all number
    13
    11
    Amylase increased
         subjects affected / exposed
    3 / 11 (27.27%)
    5 / 26 (19.23%)
         occurrences all number
    7
    38
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 11 (9.09%)
    6 / 26 (23.08%)
         occurrences all number
    22
    7
    Blood bilirubin increased
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 26 (3.85%)
         occurrences all number
    1
    1
    Blood creatinine increased
         subjects affected / exposed
    3 / 11 (27.27%)
    2 / 26 (7.69%)
         occurrences all number
    14
    4
    Blood thyroid stimulating hormone decreased
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Blood potassium increased
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Neutrophil count decreased
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Platelet count decreased
         subjects affected / exposed
    1 / 11 (9.09%)
    3 / 26 (11.54%)
         occurrences all number
    1
    4
    Weight decreased
         subjects affected / exposed
    1 / 11 (9.09%)
    3 / 26 (11.54%)
         occurrences all number
    2
    3
    Blood phosphorus increased
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Glomerular filtration rate decreased
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    3
    Lipase increased
         subjects affected / exposed
    1 / 11 (9.09%)
    6 / 26 (23.08%)
         occurrences all number
    1
    39
    Lymphocyte count decreased
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    2
    0
    Lymphocyte count increased
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Liver function test increased
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    N-terminal prohormone brain natriuretic peptide increased
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Calcium phosphate product increased
         subjects affected / exposed
    2 / 11 (18.18%)
    0 / 26 (0.00%)
         occurrences all number
    4
    0
    Renal function test abnormal
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 26 (3.85%)
         occurrences all number
    2
    2
    Transaminases increased
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Electrocardiogram ST-T segment abnormal
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Injury, poisoning and procedural complications
    Subcutaneous haematoma
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Fall
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Stoma site ulcer
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Stoma site inflammation
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Post-traumatic pain
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Procedural pain
         subjects affected / exposed
    0 / 11 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    2
    Post procedural fever
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Chest injury
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Pericardial effusion
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    2
    Sinus tachycardia
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Nervous system disorders
    Dysgeusia
         subjects affected / exposed
    1 / 11 (9.09%)
    6 / 26 (23.08%)
         occurrences all number
    1
    11
    Dizziness
         subjects affected / exposed
    0 / 11 (0.00%)
    3 / 26 (11.54%)
         occurrences all number
    0
    4
    Amnesia
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Headache
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    2
    Hyperaesthesia
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Hypoaesthesia
         subjects affected / exposed
    0 / 11 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    8
    Hypotonia
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Loss of consciousness
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Taste disorder
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    2
    Paraesthesia
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    2
    Memory impairment
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    4 / 11 (36.36%)
    4 / 26 (15.38%)
         occurrences all number
    12
    14
    Lymphopenia
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 26 (3.85%)
         occurrences all number
    3
    1
    Neutropenia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Neutrophilia
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 26 (3.85%)
         occurrences all number
    1
    1
    Leukocytosis
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    2
    Thrombocytopenia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    2
    0
    Hypereosinophilic syndrome
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    2
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Vertigo
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Eye disorders
    Cataract
         subjects affected / exposed
    0 / 11 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    2
    Blepharitis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Chalazion
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Diplopia
         subjects affected / exposed
    0 / 11 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    2
    Dry eye
         subjects affected / exposed
    0 / 11 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    2
    Eye irritation
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Keratitis
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Keratopathy
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Macular degeneration
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Lacrimation increased
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 26 (3.85%)
         occurrences all number
    1
    1
    Maculopathy
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Photopsia
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Retinal detachment
         subjects affected / exposed
    1 / 11 (9.09%)
    2 / 26 (7.69%)
         occurrences all number
    1
    2
    Retinopathy
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Vision blurred
         subjects affected / exposed
    0 / 11 (0.00%)
    4 / 26 (15.38%)
         occurrences all number
    0
    6
    Visual acuity reduced
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Detachment of retinal pigment epithelium
         subjects affected / exposed
    0 / 11 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    2
    Xerophthalmia
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 26 (3.85%)
         occurrences all number
    1
    1
    Vitreous floaters
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Visual impairment
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Corneal toxicity
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Ocular rosacea
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Detachment of macular retinal pigment epithelium
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    2
    Meibomian gland dysfunction
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    2
    Retinoschisis
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Serous retinopathy
         subjects affected / exposed
    0 / 11 (0.00%)
    4 / 26 (15.38%)
         occurrences all number
    0
    5
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Constipation
         subjects affected / exposed
    1 / 11 (9.09%)
    7 / 26 (26.92%)
         occurrences all number
    1
    8
    Colitis
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Ascites
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Aphthous ulcer
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    2
    0
    Abdominal pain
         subjects affected / exposed
    3 / 11 (27.27%)
    7 / 26 (26.92%)
         occurrences all number
    3
    7
    Diarrhoea
         subjects affected / exposed
    7 / 11 (63.64%)
    16 / 26 (61.54%)
         occurrences all number
    20
    51
    Dry mouth
         subjects affected / exposed
    3 / 11 (27.27%)
    7 / 26 (26.92%)
         occurrences all number
    3
    10
    Dyspepsia
         subjects affected / exposed
    1 / 11 (9.09%)
    4 / 26 (15.38%)
         occurrences all number
    1
    5
    Eructation
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    2
    Flatulence
         subjects affected / exposed
    0 / 11 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    2
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 26 (3.85%)
         occurrences all number
    1
    2
    Haematochezia
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Haemorrhoids
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 26 (3.85%)
         occurrences all number
    1
    1
    Inguinal hernia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Rectal haemorrhage
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Oral pain
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Oral lichen planus
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    3
    0
    Nausea
         subjects affected / exposed
    3 / 11 (27.27%)
    10 / 26 (38.46%)
         occurrences all number
    7
    15
    Stomatitis
         subjects affected / exposed
    1 / 11 (9.09%)
    2 / 26 (7.69%)
         occurrences all number
    1
    4
    Anal erythema
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Tongue erosion
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Toothache
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Vomiting
         subjects affected / exposed
    2 / 11 (18.18%)
    7 / 26 (26.92%)
         occurrences all number
    6
    7
    Rectal discharge
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Abdominal hernia
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Hepatobiliary disorders
    Hepatic function abnormal
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Hepatitis
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Hyperbilirubinaemia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    3
    0
    Hypertransaminasaemia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    2
    0
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    0 / 11 (0.00%)
    5 / 26 (19.23%)
         occurrences all number
    0
    7
    Nail disorder
         subjects affected / exposed
    1 / 11 (9.09%)
    3 / 26 (11.54%)
         occurrences all number
    1
    3
    Nail discolouration
         subjects affected / exposed
    0 / 11 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    5
    Hyperkeratosis
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Erythema
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 26 (3.85%)
         occurrences all number
    1
    1
    Eczema
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    2
    0
    Dry skin
         subjects affected / exposed
    1 / 11 (9.09%)
    5 / 26 (19.23%)
         occurrences all number
    1
    7
    Nail dystrophy
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    7
    Decubitus ulcer
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    0 / 11 (0.00%)
    4 / 26 (15.38%)
         occurrences all number
    0
    14
    Palmar erythema
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Onycholysis
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    3
    Nail hypertrophy
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Pruritus
         subjects affected / exposed
    1 / 11 (9.09%)
    5 / 26 (19.23%)
         occurrences all number
    2
    5
    Rash
         subjects affected / exposed
    2 / 11 (18.18%)
    5 / 26 (19.23%)
         occurrences all number
    10
    8
    Psoriasis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Rash macular
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    5
    0
    Rash papular
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Rash pruritic
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Seborrhoeic dermatitis
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Skin exfoliation
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Skin lesion
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Xeroderma
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Onychomadesis
         subjects affected / exposed
    0 / 11 (0.00%)
    4 / 26 (15.38%)
         occurrences all number
    0
    12
    Diabetic foot
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Nail bed inflammation
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    2 / 11 (18.18%)
    4 / 26 (15.38%)
         occurrences all number
    2
    6
    Urinary retention
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    3
    Renal pain
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Renal failure
         subjects affected / exposed
    0 / 11 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    2
    Hydronephrosis
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Nocturia
         subjects affected / exposed
    0 / 11 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    2
    Pollakiuria
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Proteinuria
         subjects affected / exposed
    1 / 11 (9.09%)
    2 / 26 (7.69%)
         occurrences all number
    1
    3
    Leukocyturia
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    2
    Renal impairment
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Hypothyroidism
         subjects affected / exposed
    2 / 11 (18.18%)
    2 / 26 (7.69%)
         occurrences all number
    2
    2
    Musculoskeletal and connective tissue disorders
    Joint swelling
         subjects affected / exposed
    0 / 11 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    2
    Groin pain
         subjects affected / exposed
    2 / 11 (18.18%)
    1 / 26 (3.85%)
         occurrences all number
    2
    1
    Flank pain
         subjects affected / exposed
    0 / 11 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    2
    Bone pain
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Back pain
         subjects affected / exposed
    4 / 11 (36.36%)
    6 / 26 (23.08%)
         occurrences all number
    5
    6
    Arthralgia
         subjects affected / exposed
    3 / 11 (27.27%)
    6 / 26 (23.08%)
         occurrences all number
    4
    14
    Muscle spasms
         subjects affected / exposed
    0 / 11 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    4
    Musculoskeletal pain
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Spinal pain
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Tendon pain
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Rotator cuff syndrome
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    2
    Pain in jaw
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Neck pain
         subjects affected / exposed
    1 / 11 (9.09%)
    3 / 26 (11.54%)
         occurrences all number
    1
    3
    Myalgia
         subjects affected / exposed
    1 / 11 (9.09%)
    2 / 26 (7.69%)
         occurrences all number
    2
    3
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Atypical pneumonia
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Conjunctivitis
         subjects affected / exposed
    1 / 11 (9.09%)
    2 / 26 (7.69%)
         occurrences all number
    2
    2
    Cystitis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    2
    0
    Diverticulitis
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Fungal skin infection
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Herpes simplex
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Influenza
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 26 (3.85%)
         occurrences all number
    1
    2
    Oesophageal candidiasis
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Onychomycosis
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    2
    Oral candidiasis
         subjects affected / exposed
    0 / 11 (0.00%)
    4 / 26 (15.38%)
         occurrences all number
    0
    5
    Paronychia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Escherichia urinary tract infection
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Urinary tract infection
         subjects affected / exposed
    4 / 11 (36.36%)
    9 / 26 (34.62%)
         occurrences all number
    8
    29
    Pyelonephritis
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Tooth abscess
         subjects affected / exposed
    0 / 11 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    2
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Anorectal infection
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Respiratory tract infection
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 26 (3.85%)
         occurrences all number
    1
    1
    Herpes dermatitis
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 26 (3.85%)
         occurrences all number
    1
    1
    Device related infection
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Oral herpes
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    3
    0
    Klebsiella urinary tract infection
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    COVID-19
         subjects affected / exposed
    1 / 11 (9.09%)
    2 / 26 (7.69%)
         occurrences all number
    2
    2
    Candida infection
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Gastrointestinal viral infection
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Metabolism and nutrition disorders
    Hypertriglyceridaemia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Hyperphosphataemia
         subjects affected / exposed
    4 / 11 (36.36%)
    15 / 26 (57.69%)
         occurrences all number
    5
    45
    Hyperkalaemia
         subjects affected / exposed
    0 / 11 (0.00%)
    4 / 26 (15.38%)
         occurrences all number
    0
    4
    Hyperglycaemia
         subjects affected / exposed
    2 / 11 (18.18%)
    1 / 26 (3.85%)
         occurrences all number
    2
    1
    Hypercholesterolaemia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Hypercalcaemia
         subjects affected / exposed
    1 / 11 (9.09%)
    3 / 26 (11.54%)
         occurrences all number
    1
    5
    Dehydration
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    2
    Hypocalcaemia
         subjects affected / exposed
    0 / 11 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    2
    Hypomagnesaemia
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Hyperlipasaemia
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 26 (3.85%)
         occurrences all number
    6
    1
    Hypercreatininaemia
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 26 (3.85%)
         occurrences all number
    1
    2
    Decreased appetite
         subjects affected / exposed
    3 / 11 (27.27%)
    8 / 26 (30.77%)
         occurrences all number
    7
    12
    Metabolic acidosis
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Hypophosphataemia
         subjects affected / exposed
    1 / 11 (9.09%)
    2 / 26 (7.69%)
         occurrences all number
    1
    15
    Hyponatraemia
         subjects affected / exposed
    0 / 11 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    5

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    04 Dec 2018
    - Immune-related nephritis was added as new identified risk for atezolizumab - Management guideline of rogaratinib-induced hyperphosphatemia was updated. - The option of transferring patients to a roll-over study was included. - Wording was clarified for the tumor biopsy procedure for biomarker testing.
    10 Feb 2021
    - Immune-related myositis and severe cutaneous adverse reactions were added as new identified risks for atezolizumab together with respective management guidelines . - The option of continuing post-study therapy in any other form of continued study drug supply with no cost to the patient was included.
    04 Oct 2021
    - After primary completion, study procedures were reduced to decrease burden to patients and sites - The updated schedule of events is intended to mimic standard of care - Immune-related myositis and severe cutaneous adverse reactions were added as new identified risks for atezolizumab - After primary completion, pregnancy tests were no longer required because there were no female patients of childbearing potential left in the study - The interval for tumor assessments was prolonged during the treatment and active follow-up periods - The decision to not conduct Part B of the study was communicated on 25 OCT 2021 as part of the submission of this amendment to ethical committees/health authorities, and sites, and duly implemented under this amendment.
    09 Nov 2022
    - Immune-mediated pericardial disorders was added as new identified risk - Management guideliens for atezolizumab-specific adverse events were revised - active and long-term follow-ups were concluded.
    23 May 2023
    - Immune-mediated myelitis and immune-mediated facial paresis were added as new identified risks for atezolizumab - Management guidelines were revised for atezolizumab-specific adverse events.

    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

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/36240478
    http://www.ncbi.nlm.nih.gov/pubmed/39298147
    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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