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    Clinical Trial Results:
    An Open-Label Phase 2 Study of Surufatinib in Patients with Neuroendocrine Tumors in Europe

    Summary
    EudraCT number
    		 2020-006118-19
    Trial protocol
    		 FR   DE   NO   IT   ES  
    Global end of trial date
    06 Sep 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    31 Aug 2025
    First version publication date
    31 Aug 2025
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    2020-012-00EU1
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04579679
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    HUTCHMED Limited
    Sponsor organisation address
    Building 4, 720 Cailun Road China (Shanghai) Pilot Free Trade Zone, Shanghai, China, 201203
    Public contact
    Nick Lawn, HUTCHMED International Corporation, +44 7826 422448, nickl@hutch-med.com
    Scientific contact
    William Schelman, HUTCHMED International Corporation, +44 1.973.306.4490, williams@hutch-med.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
    15 Oct 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    06 Sep 2024
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To evaluate the anti-tumor activity of surufatinib in patients with low- to intermediate-grade (Grade 1 or Grade 2), well-differentiated neuroendocrine tumors (NET).
    Protection of trial subjects
    This study was conducted in accordance with the protocol, the ethical principles derived from international guidelines, including the Declaration of Helsinki and/or all relevant federal regulations in compliance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Harmonized Tripartite Guideline, Council for International Organizations of Medical Sciences International Ethical Guidelines, Good Clinical Practice guidelines, and according to the appropriate regulatory requirements in the countries where the study was conducted.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    13 Aug 2021
    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
    Norway: 3
    Country: Number of subjects enrolled
    Spain: 30
    Country: Number of subjects enrolled
    France: 15
    Country: Number of subjects enrolled
    Italy: 21
    Country: Number of subjects enrolled
    United Kingdom: 3
    Country: Number of subjects enrolled
    United States: 6
    Worldwide total number of subjects
    78
    EEA total number of subjects
    69
    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)
    38
    From 65 to 84 years
    40
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 This Phase 2, open-label, multi-center study was conducted in patients with locally advanced or metastatic low to intermediate grade (Grade 1 or Grade 2), well-differentiated NETs. The study was terminated early based on strategic re-evaluation of clinical development program for surufatinib and not due to any safety concerns.

    Pre-assignment
    Screening details
    		 The study enrolled patients in 4 cohorts of varying NETs, as follows: • Cohort A - NET of lung origin (NET, lung) • Cohort B - NET of small bowel origin (NET, small bowel) • Cohort C - NET of non-small bowel, non-pancreas, and non-lung origin (NET, other) • Cohort D - NET of any origin (NET, any).

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Cohort A (NET, Lung)
    Arm description
    		 Patients with NET of lung origin received surufatinib 300 milligrams (mg) orally once daily (QD) in treatment cycles of 28 days starting on Cycle (C)1 Day (D)1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Surufatinib
    Investigational medicinal product code
    Other name
    HMPL-012
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    Surufatinib 300 mg was administered orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.

    Arm title
    		 Cohort B (NET, Small Bowel)
    Arm description
    		 Patients with NET of small bowel origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Surufatinib
    Investigational medicinal product code
    Other name
    HMPL-012
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    Surufatinib 300 mg was administered orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.

    Arm title
    		 Cohort C (NET, Other)
    Arm description
    		 Patients with NET of non-small bowel, non-pancreas, and non-lung origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Surufatinib
    Investigational medicinal product code
    Other name
    HMPL-012
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    Surufatinib 300 mg was administered orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.

    Arm title
    		 Cohort D (NET, Any)
    Arm description
    		 Patients with NET of any origin received a single dose of drug cocktail (midazolam 2.5 mg, fexofenadine 30 mg and rosuvastatin 10 mg) on Day -2 followed by surufatinib 300 mg orally QD from C1D1 to C1D14. On C1D15, a single dose of surufatinib 300 mg and a single dose of drug cocktail as above was administered. Patients received surufatinib 300 mg orally QD from C1D16 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Surufatinib
    Investigational medicinal product code
    Other name
    HMPL-012
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    Surufatinib 300 mg was administered orally QD as mentioned in the protocol.

    Investigational medicinal product name
    Midazolam
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral liquid
    Routes of administration
    Oral use
    Dosage and administration details
    Midazolam 2.5 mg was administered as a part of drug cocktail as per protocol to patients in Cohort D.

    Investigational medicinal product name
    Fexofenadine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral suspension, Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Fexofenadine 30 mg was administered as a part of drug cocktail as per protocol to patients in Cohort D.

    Investigational medicinal product name
    Rosuvastatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Rosuvastatin 10 mg was administered as a part of drug cocktail as per protocol to patients in Cohort D.

    Number of subjects in period 1
    		Cohort A (NET, Lung) Cohort B (NET, Small Bowel) Cohort C (NET, Other) Cohort D (NET, Any)
    Started
    20
    32
    20
    6
    Completed
    0
    1
    0
    2
    Not completed
    20
    31
    20
    4
         Consent withdrawn by subject
    1
    1
    2
    4
         Physician decision
    -
    -
    1
    -
         Adverse event, non-fatal
    -
    4
    -
    -
         Death
    2
    2
    2
    -
         New Antitumor Therapy
    6
    4
    7
    -
         Study terminated by sponsor
    2
    7
    1
    -
         Disease Progression
    9
    13
    7
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Cohort A (NET, Lung)
    Reporting group description
    		 Patients with NET of lung origin received surufatinib 300 milligrams (mg) orally once daily (QD) in treatment cycles of 28 days starting on Cycle (C)1 Day (D)1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.

    Reporting group title
    Cohort B (NET, Small Bowel)
    Reporting group description
    		 Patients with NET of small bowel origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.

    Reporting group title
    Cohort C (NET, Other)
    Reporting group description
    		 Patients with NET of non-small bowel, non-pancreas, and non-lung origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.

    Reporting group title
    Cohort D (NET, Any)
    Reporting group description
    		 Patients with NET of any origin received a single dose of drug cocktail (midazolam 2.5 mg, fexofenadine 30 mg and rosuvastatin 10 mg) on Day -2 followed by surufatinib 300 mg orally QD from C1D1 to C1D14. On C1D15, a single dose of surufatinib 300 mg and a single dose of drug cocktail as above was administered. Patients received surufatinib 300 mg orally QD from C1D16 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.

    Reporting group values
    		 Cohort A (NET, Lung) Cohort B (NET, Small Bowel) Cohort C (NET, Other) Cohort D (NET, Any) Total
    Number of subjects
    		 20 32 20 6 78
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 63.5 ( 12.77 ) 62.1 ( 10.44 ) 57.3 ( 15.52 ) 63.5 ( 7.40 ) -
    Gender categorical
    Units: Subjects
        Female
    		 7 20 9 4 40
        Male
    		 13 12 11 2 38
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 0 1 0 0 1
        Black or African American
    		 0 0 0 3 3
        White
    		 15 28 13 3 59
        Not Reported
    		 4 1 7 0 12
        Other
    		 0 1 0 0 1
        Missing
    		 1 1 0 0 2
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 0 3 0 0 3
        Not Hispanic or Latino
    		 15 26 13 6 60
        Unknown or Not Reported
    		 5 3 7 0 15

    End points

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    End points reporting groups
    Reporting group title
    Cohort A (NET, Lung)
    Reporting group description
    		 Patients with NET of lung origin received surufatinib 300 milligrams (mg) orally once daily (QD) in treatment cycles of 28 days starting on Cycle (C)1 Day (D)1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.

    Reporting group title
    Cohort B (NET, Small Bowel)
    Reporting group description
    		 Patients with NET of small bowel origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.

    Reporting group title
    Cohort C (NET, Other)
    Reporting group description
    		 Patients with NET of non-small bowel, non-pancreas, and non-lung origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.

    Reporting group title
    Cohort D (NET, Any)
    Reporting group description
    		 Patients with NET of any origin received a single dose of drug cocktail (midazolam 2.5 mg, fexofenadine 30 mg and rosuvastatin 10 mg) on Day -2 followed by surufatinib 300 mg orally QD from C1D1 to C1D14. On C1D15, a single dose of surufatinib 300 mg and a single dose of drug cocktail as above was administered. Patients received surufatinib 300 mg orally QD from C1D16 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.

    Primary: Disease Control Rate (DCR)

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    End point title
    		 Disease Control Rate (DCR) [1]
    End point description
    The DCR was defined as the percentage of patients who achieved a best overall response (BOR) of complete response (CR), partial response (PR) or stable disease (SD) as determined by the Investigator using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. The CR was defined as disappearance of all target lesions. The PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum on study. The efficacy analysis set included all patients who received at least 1 dose of surufatinib and had at least 1 post-baseline tumor assessment.
    End point type
    Primary
    End point timeframe
    RECIST assessments performed at screening (within 28 days before start of study drug), every 8 weeks for the first 24 weeks from C1D1, then every 12 weeks thereafter until the occurrence of disease progression, up to approximately 36 months
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: As the endpoint is descriptive in nature, no statistical analysis is presented.
    End point values
    		 Cohort A (NET, Lung) Cohort B (NET, Small Bowel) Cohort C (NET, Other) Cohort D (NET, Any)
    Number of subjects analysed
    20
    31
    19
    5
    Units: percentage of participants
        number (confidence interval 95%)
    95.0 (75.1 to 99.9)
    90.3 (74.2 to 98.0)
    89.5 (66.9 to 98.7)
    100 (47.8 to 100)
    No statistical analyses for this end point

    Secondary: Plasma Concentrations of Surufatinib

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    End point title
    		 Plasma Concentrations of Surufatinib
    End point description
    Blood samples were collected at specified timepoints to obtain plasma concentrations of surufatinib at steady state on Cycle 1 Day 15. The pharmacokinetic (PK) analysis set included all patients who received at least 1 dose of the study drug and had at least 1 measurable plasma concentration data point for at least 1 PK analyte without protocol violations or events with potential to affect the PK concentration. Here, n=only those participants with data collected at specified timepoints and 99999= no data as there were no participants analyzed for that timepoint for that cohort.
    End point type
    Secondary
    End point timeframe
    Cohorts A, B and C: Pre-dose and 1, 2, 3, 4 hours post-dose on Cycle 1 Day 15; Cohort D: Pre-dose and 30 minutes, 1, 2, 3, 4, 5, 6, 8 and 10 hours post-dose on Cycle 1 Day 15
    End point values
    		 Cohort A (NET, Lung) Cohort B (NET, Small Bowel) Cohort C (NET, Other) Cohort D (NET, Any)
    Number of subjects analysed
    17
    29
    18
    6
    Units: nanogram/milliliter
    geometric mean (geometric coefficient of variation)
        Pre-dose (n=17,25,18,6)
    73.123 ( 70.1 )
    57.593 ( 136.8 )
    49.258 ( 54.7 )
    28.913 ( 130.5 )
        30 minutes post-dose (n=0,0,0,6)
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    50.439 ( 190.5 )
        1 hour post-dose (n=17,29,15,6)
    130.456 ( 118.3 )
    96.163 ( 115.2 )
    101.464 ( 125.6 )
    129.719 ( 303.6 )
        2 hours post-dose (n=17,27,18,6)
    234.498 ( 122.1 )
    174.799 ( 138.1 )
    194.654 ( 80.5 )
    321.942 ( 99.9 )
        3 hours post-dose (n=17,29,18,6)
    287.237 ( 95.0 )
    250.348 ( 101.8 )
    245.379 ( 55.1 )
    477.653 ( 118.6 )
        4 hours post-dose (n=17,28,17,6)
    293.236 ( 85.6 )
    268.619 ( 65.9 )
    232.657 ( 42.6 )
    389.597 ( 102.8 )
        5 hours post-dose (n=0,0,0,6)
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    357.045 ( 105.4 )
        6 hours post-dose (n=0,0,0,6)
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    280.691 ( 105.2 )
        8 hours post-dose (n=0,0,0,6)
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    202.345 ( 102.7 )
        10 hours post-dose (n=0,0,0,4)
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    174.079 ( 84.1 )
    No statistical analyses for this end point

    Secondary: Number of Patients With Potentially Clinically Significant Corrected QT Interval (QTc) During Treatment

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    End point title
    		 Number of Patients With Potentially Clinically Significant Corrected QT Interval (QTc) During Treatment
    End point description
    The QT interval data was corrected for heart rate using 2 correction methods (Fridericia – QTcF and Bazett – QTcB). The treatment period was defined as the period from first administration of study drug up 30 days after last administration. The safety analysis set included all patients who received at least 1 dose of surufatinib. Here, n= only those patients with data collected for specified categories. msec=milliseconds, IFB=increase from baseline.
    End point type
    Secondary
    End point timeframe
    From the first dose of study drug (Day 1) up to 30 days after last dose of study drug, approximately 33 months
    End point values
    		 Cohort A (NET, Lung) Cohort B (NET, Small Bowel) Cohort C (NET, Other) Cohort D (NET, Any)
    Number of subjects analysed
    19
    31
    19
    6
    Units: participants
        QTcF: >450 msec to <=480 msec (n=19,31,18,6)
    0
    2
    0
    2
        QTcF: >480 msec to <=500 msec (n=19,31,18,6)
    0
    4
    1
    0
        QTcF: >500 msec (n=19,31,18,6)
    0
    0
    0
    1
        QTcF: IFB >30 msec to <=60 msec (n=19,31,18,6)
    4
    2
    1
    1
        QTcF: IFB >60 msec (n=19,31,18,6)
    0
    2
    0
    1
        QTcB: >450 msec to <=480 msec (n=19,31,19,6)
    3
    6
    3
    4
        QTcB: >480 msec to <=500 msec (n=19,31,19,6)
    0
    1
    0
    1
        QTcB: >500 msec (n=19,31,19,6)
    0
    1
    1
    1
        QTcB: IFB >30 msec to <=60 msec (n=19,31,19,6)
    2
    7
    4
    1
        QTcB: IFB >60 msec (n=19,31,19,6)
    1
    2
    0
    1
    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
    The ORR was defined as the percentage of patients with a BOR of CR or PR as determined by the Investigator using RECIST v1.1. The CR was defined as disappearance of all target lesions. The PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. The efficacy analysis set included all patients who received at least 1 dose of surufatinib and had at least 1 post-baseline tumor assessment.
    End point type
    Secondary
    End point timeframe
    RECIST assessments performed at screening (within 28 days before start of study drug), every 8 weeks for the first 24 weeks from C1D1, then every 12 weeks thereafter until the occurrence of disease progression, up to approximately 36 months
    End point values
    		 Cohort A (NET, Lung) Cohort B (NET, Small Bowel) Cohort C (NET, Other) Cohort D (NET, Any)
    Number of subjects analysed
    20
    31
    19
    5
    Units: percentage of participants
        number (confidence interval 95%)
    15.0 (3.2 to 37.9)
    16.1 (5.5 to 33.7)
    5.3 (0.1 to 26.0)
    20.0 (0.5 to 71.6)
    No statistical analyses for this end point

    Secondary: Time to Response (TTR)

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    End point title
    		 Time to Response (TTR)
    End point description
    The TTR was defined as the time from the start of study drug until the date of first documented objective response, either CR or PR (whichever was recorded first) according to RECIST v.1.1 for responders only. The CR was defined as disappearance of all target lesions. The PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. The efficacy analysis set included all patients who received at least 1 dose of surufatinib and had at least 1 post-baseline tumor assessment. Only those patients who achieved CR/PR (responders) were included in the analysis.
    End point type
    Secondary
    End point timeframe
    RECIST assessments performed at screening (within 28 days before start of study drug), every 8 weeks for the first 24 weeks from C1D1, then every 12 weeks thereafter until the occurrence of disease progression, up to approximately 36 months
    End point values
    		 Cohort A (NET, Lung) Cohort B (NET, Small Bowel) Cohort C (NET, Other) Cohort D (NET, Any)
    Number of subjects analysed
    3
    5
    1
    1
    Units: months
        median (full range (min-max))
    2.1 (1.6 to 5.3)
    3.7 (1.8 to 14.2)
    11.1 (11.1 to 11.1)
    13.6 (13.6 to 13.6)
    No statistical analyses for this end point

    Secondary: Duration of Response (DOR)

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    End point title
    		 Duration of Response (DOR)
    End point description
    The DoR was defined as the time from the first time that the objective response reached CR or PR, whichever came first (and later confirmed), until the occurrence of PD or death.CR was defined as disappearance of all target lesions.PR was defined as at least 30% decrease in sum of diameters of target lesions, taking as reference baseline sum of diameters. PD was defined as at least 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study (nadir), including baseline. In addition to the relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 millimeters. Appearance of 1 or more new lesions was also considered progression. Analysis was performed on efficacy analysis set. Only patients with PR or CR (responders) were included in the analysis. 55555=not estimable due to insufficient number of patients with events at study closure;-22222 and 22222=cannot be calculated for 1 patient.
    End point type
    Secondary
    End point timeframe
    RECIST assessments performed at screening (within 28 days before start of study drug), every 8 weeks for the first 24 weeks from C1D1, then every 12 weeks thereafter until the occurrence of disease progression, up to approximately 36 months
    End point values
    		 Cohort A (NET, Lung) Cohort B (NET, Small Bowel) Cohort C (NET, Other) Cohort D (NET, Any)
    Number of subjects analysed
    3
    5
    1
    1
    Units: months
        median (confidence interval 95%)
    16.9 (8.6 to 55555)
    15.4 (3.7 to 55555)
    5.6 (-22222 to 22222)
    55555 (55555 to 55555)
    No statistical analyses for this end point

    Secondary: Progression-Free Survival (PFS)

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    End point title
    		 Progression-Free Survival (PFS)
    End point description
    The PFS was defined as the time from the start of study drug until the first objective PD as defined by RECIST v1.1 or death, whichever came first. The PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (nadir), including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters. The appearance of 1 or more new lesions was also considered progression. The safety analysis set included all patients who received at least 1 dose of surufatinib. 55555=not estimable due to insufficient number of patients with events at study closure.
    End point type
    Secondary
    End point timeframe
    RECIST assessments performed at screening (within 28 days before start of study drug), every 8 weeks for the first 24 weeks from C1D1, then every 12 weeks thereafter until the occurrence of disease progression, up to approximately 36 months
    End point values
    		 Cohort A (NET, Lung) Cohort B (NET, Small Bowel) Cohort C (NET, Other) Cohort D (NET, Any)
    Number of subjects analysed
    20
    32
    20
    6
    Units: months
        median (confidence interval 95%)
    10.2 (5.4 to 16.6)
    19.2 (8.3 to 55555)
    11.4 (5.7 to 16.7)
    9.8 (7.2 to 55555)
    No statistical analyses for this end point

    Secondary: Cohort D: Geometric Least Squares (LS) Mean Ratio of Cytochrome P450 (CYP3A4), P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) Substrates at Cycle 1 Day 15 to Baseline

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    End point title
    		 Cohort D: Geometric Least Squares (LS) Mean Ratio of Cytochrome P450 (CYP3A4), P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) Substrates at Cycle 1 Day 15 to Baseline [2]
    End point description
    Participants were administered midazolam, fexofenadine and rosuvastatin (as part of the drug cocktail) as a single dose on Day -2 (without surufatinib) and on Cycle 1 Day 15 (with surufatinib). Separate blood samples were collected for measurement of plasma concentrations of each probe substrate and surufatinib. Probe substrate of midazolam was CYP3A4, fexofenadine was P-gp and rosuvastatin was BCRP. Ratio of LS Mean for maximum plasma concentration (Cmax), area under the plasma concentration-time curve from time 0 to time of last measurable concentration (AUC0-t) and area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf) are presented as Cycle 1 Day 15/Day -2. The PK evaluable population included all patients who received at least 1 dose of the study drug and had sufficient concentration data to derive at least 1 PK parameter.
    End point type
    Secondary
    End point timeframe
    Baseline (Day -2) and Cycle 1 Day 15
    Notes
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only Cohort D is evaluated for this endpoint.
    End point values
    		 Cohort D (NET, Any)
    Number of subjects analysed
    6
    Units: Ratio of geometric LS mean
    number (confidence interval 90%)
        Midazolam (CYP3A4 substrate), Cmax
    1.69 (1.20 to 2.39)
        Midazolam (CYP3A4 substrate), AUC0-t
    1.70 (1.14 to 2.52)
        Midazolam (CYP3A4 substrate), AUC0-inf
    1.71 (1.16 to 2.53)
        Fexofenadine (P-gp substrate), Cmax
    2.03 (1.51 to 2.75)
        Fexofenadine (P-gp substrate), AUC0-t
    2.12 (1.65 to 2.73)
        Fexofenadine (P-gp substrate), AUC0-inf
    2.14 (1.64 to 2.78)
        Rosuvastatin (BCRP substrate), Cmax
    2.23 (1.59 to 3.14)
        Rosuvastatin (BCRP substrate), AUC0-t
    2.13 (1.31 to 3.48)
        Rosuvastatin (BCRP substrate), AUC0-inf
    2.23 (1.23 to 4.01)
    No statistical analyses for this end point

    Secondary: Number of Patients With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

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    End point title
    		 Number of Patients With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
    End point description
    An AE is any untoward medical occurrence in a clinical study patient temporally associated with the use of a study drug, whether or not considered related to the drug. An SAE was an AE that resulted in any of the following outcomes: death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; a congenital anomaly/birth defect or was any important medical event. TEAEs were defined as any AEs that started or worsened in severity on or after the first administration date of study drug and no later than 30 (+7) days after the last administration date of study drug or initiation of new anti-tumor therapy (whichever occurred first). The safety analysis set included all patients who received at least 1 dose of surufatinib.
    End point type
    Secondary
    End point timeframe
    From the first dose of study drug (Day 1) up to 30 days after last dose of study drug, approximately 33 months
    End point values
    		 Cohort A (NET, Lung) Cohort B (NET, Small Bowel) Cohort C (NET, Other) Cohort D (NET, Any)
    Number of subjects analysed
    20
    32
    20
    6
    Units: participants
        TEAEs
    20
    32
    20
    6
        TESAEs
    4
    12
    8
    2
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were collected from the first dose of study drug (Day 1) up to 30 days after last dose of study drug, approximately 33 months. Deaths were collected from screening (Day -28) up to end of follow-up, approximately 36 months
    Adverse event reporting additional description
    The safety analysis set included all patients who received at least 1 dose of surufatinib.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    27.0
    Reporting groups
    Reporting group title
    Cohort A (NET, Lung)
    Reporting group description
    		 Patients with NET of lung origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.

    Reporting group title
    Cohort B (NET, Small Bowel)
    Reporting group description
    		 Patients with NET of small bowel origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.

    Reporting group title
    Cohort C (NET, Other)
    Reporting group description
    		 Patients with NET of non-small bowel, non-pancreas, and non-lung origin received surufatinib 300 mg orally QD in treatment cycles of 28 days starting on C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.

    Reporting group title
    Cohort D (NET, Any)
    Reporting group description
    		 Patients with NET of any origin received a single dose of drug cocktail (midazolam 2.5 mg, fexofenadine 30 mg and rosuvastatin 10 mg) on Day -2 followed by surufatinib 300 mg orally QD from C1D1 to C1D14. On C1D15, a single dose of surufatinib 300 mg and a single dose of drug cocktail as above was administered. Patients received surufatinib 300 mg orally QD from C1D16 until disease progression, death, unacceptable toxicity, withdrawal of consent or lost to follow-up.

    Serious adverse events
    		 Cohort A (NET, Lung) Cohort B (NET, Small Bowel) Cohort C (NET, Other) Cohort D (NET, Any)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 20 (20.00%)
    12 / 32 (37.50%)
    8 / 20 (40.00%)
    2 / 6 (33.33%)
         number of deaths (all causes)
    2
    2
    2
    0
         number of deaths resulting from adverse events
    0
    1
    1
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Glioblastoma
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 32 (0.00%)
    1 / 20 (5.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malignant neoplasm progression
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 32 (3.13%)
    1 / 20 (5.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    Tumour haemorrhage
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 32 (0.00%)
    1 / 20 (5.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Haematoma
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 32 (0.00%)
    1 / 20 (5.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertensive emergency
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 32 (3.13%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    General physical health deterioration
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 32 (6.25%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 32 (0.00%)
    0 / 20 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 32 (3.13%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Multisystem inflammatory syndrome
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 32 (0.00%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthmatic crisis
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 32 (0.00%)
    1 / 20 (5.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 32 (0.00%)
    0 / 20 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Blood bilirubin increased
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 32 (0.00%)
    0 / 20 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood creatinine increased
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 32 (0.00%)
    0 / 20 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac function test abnormal
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 32 (0.00%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Femur fracture
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 32 (3.13%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 32 (0.00%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 32 (0.00%)
    1 / 20 (5.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 32 (6.25%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Balance disorder
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 32 (0.00%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 32 (3.13%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 32 (3.13%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestinal obstruction
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 32 (3.13%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 32 (6.25%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 32 (3.13%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Biliary obstruction
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 32 (3.13%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic function abnormal
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 32 (3.13%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperbilirubinaemia
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 32 (0.00%)
    1 / 20 (5.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal artery dissection
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 32 (3.13%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 32 (0.00%)
    1 / 20 (5.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal infarct
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 32 (3.13%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 32 (0.00%)
    0 / 20 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 32 (0.00%)
    0 / 20 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 32 (0.00%)
    1 / 20 (5.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Failure to thrive
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 32 (0.00%)
    0 / 20 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 32 (3.13%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Cohort A (NET, Lung) Cohort B (NET, Small Bowel) Cohort C (NET, Other) Cohort D (NET, Any)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    20 / 20 (100.00%)
    32 / 32 (100.00%)
    20 / 20 (100.00%)
    6 / 6 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 32 (0.00%)
    0 / 20 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Vascular disorders
    Hypertension
         subjects affected / exposed
    14 / 20 (70.00%)
    16 / 32 (50.00%)
    15 / 20 (75.00%)
    3 / 6 (50.00%)
         occurrences all number
    32
    41
    35
    4
    Flushing
         subjects affected / exposed
    1 / 20 (5.00%)
    2 / 32 (6.25%)
    2 / 20 (10.00%)
    0 / 6 (0.00%)
         occurrences all number
    3
    2
    2
    0
    Hypotension
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 32 (6.25%)
    1 / 20 (5.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    3
    1
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    14 / 20 (70.00%)
    20 / 32 (62.50%)
    13 / 20 (65.00%)
    0 / 6 (0.00%)
         occurrences all number
    49
    47
    22
    0
    Pyrexia
         subjects affected / exposed
    6 / 20 (30.00%)
    7 / 32 (21.88%)
    4 / 20 (20.00%)
    0 / 6 (0.00%)
         occurrences all number
    11
    12
    4
    0
    Fatigue
         subjects affected / exposed
    1 / 20 (5.00%)
    10 / 32 (31.25%)
    1 / 20 (5.00%)
    3 / 6 (50.00%)
         occurrences all number
    1
    17
    6
    4
    Oedema peripheral
         subjects affected / exposed
    3 / 20 (15.00%)
    7 / 32 (21.88%)
    3 / 20 (15.00%)
    0 / 6 (0.00%)
         occurrences all number
    4
    9
    3
    0
    Mucosal inflammation
         subjects affected / exposed
    2 / 20 (10.00%)
    2 / 32 (6.25%)
    1 / 20 (5.00%)
    0 / 6 (0.00%)
         occurrences all number
    3
    3
    1
    0
    Influenza like illness
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 32 (0.00%)
    2 / 20 (10.00%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    2
    1
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 32 (6.25%)
    0 / 20 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    2
    0
    1
    Oedema
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 32 (6.25%)
    1 / 20 (5.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    1
    0
    Peripheral swelling
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 32 (0.00%)
    0 / 20 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Reproductive system and breast disorders
    Erectile dysfunction
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 32 (0.00%)
    1 / 20 (5.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Genital hypoaesthesia
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 32 (0.00%)
    1 / 20 (5.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Heavy menstrual bleeding
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 32 (3.13%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Pelvic pain
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 32 (3.13%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Vaginal haemorrhage
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 32 (3.13%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    6 / 20 (30.00%)
    1 / 32 (3.13%)
    4 / 20 (20.00%)
    1 / 6 (16.67%)
         occurrences all number
    9
    2
    4
    1
    Dyspnoea
         subjects affected / exposed
    1 / 20 (5.00%)
    3 / 32 (9.38%)
    1 / 20 (5.00%)
    1 / 6 (16.67%)
         occurrences all number
    1
    4
    1
    1
    Epistaxis
         subjects affected / exposed
    2 / 20 (10.00%)
    2 / 32 (6.25%)
    2 / 20 (10.00%)
    0 / 6 (0.00%)
         occurrences all number
    4
    2
    2
    0
    Dyspnoea exertional
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 32 (0.00%)
    2 / 20 (10.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    2
    0
    Haemoptysis
         subjects affected / exposed
    2 / 20 (10.00%)
    1 / 32 (3.13%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    3
    2
    0
    0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    0 / 20 (0.00%)
    5 / 32 (15.63%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    5
    0
    0
    Investigations
    Aspartate aminotransferase increased
         subjects affected / exposed
    3 / 20 (15.00%)
    8 / 32 (25.00%)
    2 / 20 (10.00%)
    0 / 6 (0.00%)
         occurrences all number
    6
    14
    3
    0
    Blood bilirubin increased
         subjects affected / exposed
    5 / 20 (25.00%)
    2 / 32 (6.25%)
    4 / 20 (20.00%)
    1 / 6 (16.67%)
         occurrences all number
    12
    5
    11
    1
    Alanine aminotransferase increased
         subjects affected / exposed
    2 / 20 (10.00%)
    6 / 32 (18.75%)
    2 / 20 (10.00%)
    0 / 6 (0.00%)
         occurrences all number
    2
    13
    3
    0
    Weight decreased
         subjects affected / exposed
    5 / 20 (25.00%)
    2 / 32 (6.25%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    5
    2
    0
    0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    3 / 20 (15.00%)
    2 / 32 (6.25%)
    0 / 20 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    5
    4
    0
    1
    Blood creatinine increased
         subjects affected / exposed
    3 / 20 (15.00%)
    1 / 32 (3.13%)
    2 / 20 (10.00%)
    0 / 6 (0.00%)
         occurrences all number
    3
    2
    4
    0
    Platelet count decreased
         subjects affected / exposed
    1 / 20 (5.00%)
    3 / 32 (9.38%)
    0 / 20 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    1
    3
    0
    2
    Amylase increased
         subjects affected / exposed
    3 / 20 (15.00%)
    0 / 32 (0.00%)
    0 / 20 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    3
    0
    0
    1
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 20 (5.00%)
    2 / 32 (6.25%)
    1 / 20 (5.00%)
    0 / 6 (0.00%)
         occurrences all number
    2
    4
    2
    0
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 32 (3.13%)
    2 / 20 (10.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    2
    0
    Blood thyroid stimulating hormone increased
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 32 (0.00%)
    1 / 20 (5.00%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    1
    1
    Bilirubin conjugated increased
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 32 (0.00%)
    0 / 20 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Blood pressure increased
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 32 (0.00%)
    0 / 20 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Troponin increased
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 32 (0.00%)
    0 / 20 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 32 (3.13%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Fall
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 32 (0.00%)
    1 / 20 (5.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Head injury
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 32 (0.00%)
    1 / 20 (5.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Muscle rupture
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 32 (0.00%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Tooth fracture
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 32 (3.13%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Post procedural haemorrhage
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 32 (3.13%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Sunburn
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 32 (0.00%)
    1 / 20 (5.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Joint dislocation
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 32 (3.13%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Foot fracture
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 32 (3.13%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Radius fracture
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 32 (0.00%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Limb injury
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 32 (0.00%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    2 / 20 (10.00%)
    0 / 32 (0.00%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Tachycardia
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 32 (0.00%)
    0 / 20 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    6 / 20 (30.00%)
    4 / 32 (12.50%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    8
    5
    0
    0
    Dizziness
         subjects affected / exposed
    1 / 20 (5.00%)
    3 / 32 (9.38%)
    1 / 20 (5.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    3
    1
    0
    Sciatica
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 32 (3.13%)
    4 / 20 (20.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    7
    0
    Dysgeusia
         subjects affected / exposed
    1 / 20 (5.00%)
    2 / 32 (6.25%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    4
    0
    0
    Tremor
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 32 (6.25%)
    1 / 20 (5.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    3
    2
    0
    Hypoaesthesia
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 32 (0.00%)
    2 / 20 (10.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 20 (10.00%)
    5 / 32 (15.63%)
    3 / 20 (15.00%)
    1 / 6 (16.67%)
         occurrences all number
    2
    8
    8
    2
    Leukocytosis
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 32 (3.13%)
    1 / 20 (5.00%)
    2 / 6 (33.33%)
         occurrences all number
    0
    1
    1
    2
    Thrombocytopenia
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 32 (3.13%)
    1 / 20 (5.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    1
    1
    Ear and labyrinth disorders
    Tinnitus
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 32 (3.13%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Vertigo
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 32 (3.13%)
    1 / 20 (5.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Acute vestibular syndrome
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 32 (0.00%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Eye disorders
    Diplopia
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 32 (6.25%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    11 / 20 (55.00%)
    22 / 32 (68.75%)
    13 / 20 (65.00%)
    2 / 6 (33.33%)
         occurrences all number
    20
    82
    24
    4
    Nausea
         subjects affected / exposed
    5 / 20 (25.00%)
    10 / 32 (31.25%)
    4 / 20 (20.00%)
    3 / 6 (50.00%)
         occurrences all number
    7
    30
    6
    3
    Abdominal pain
         subjects affected / exposed
    2 / 20 (10.00%)
    11 / 32 (34.38%)
    3 / 20 (15.00%)
    0 / 6 (0.00%)
         occurrences all number
    4
    23
    3
    0
    Vomiting
         subjects affected / exposed
    6 / 20 (30.00%)
    5 / 32 (15.63%)
    4 / 20 (20.00%)
    1 / 6 (16.67%)
         occurrences all number
    8
    19
    6
    2
    Constipation
         subjects affected / exposed
    2 / 20 (10.00%)
    4 / 32 (12.50%)
    5 / 20 (25.00%)
    0 / 6 (0.00%)
         occurrences all number
    3
    4
    6
    0
    Abdominal pain upper
         subjects affected / exposed
    2 / 20 (10.00%)
    3 / 32 (9.38%)
    3 / 20 (15.00%)
    0 / 6 (0.00%)
         occurrences all number
    2
    3
    3
    0
    Flatulence
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 32 (6.25%)
    3 / 20 (15.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    3
    3
    0
    Stomatitis
         subjects affected / exposed
    2 / 20 (10.00%)
    1 / 32 (3.13%)
    2 / 20 (10.00%)
    0 / 6 (0.00%)
         occurrences all number
    4
    1
    2
    0
    Dry mouth
         subjects affected / exposed
    1 / 20 (5.00%)
    2 / 32 (6.25%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    5
    0
    0
    Dyspepsia
         subjects affected / exposed
    2 / 20 (10.00%)
    1 / 32 (3.13%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    2
    1
    0
    0
    Abdominal distension
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 32 (3.13%)
    0 / 20 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    2
    0
    1
    Abdominal pain lower
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 32 (0.00%)
    0 / 20 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    0
    1
    Hepatobiliary disorders
    Hyperbilirubinaemia
         subjects affected / exposed
    1 / 20 (5.00%)
    2 / 32 (6.25%)
    0 / 20 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    1
    3
    0
    3
    Hypertransaminasaemia
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 32 (0.00%)
    0 / 20 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Skin and subcutaneous tissue disorders
    Dry skin
         subjects affected / exposed
    1 / 20 (5.00%)
    3 / 32 (9.38%)
    2 / 20 (10.00%)
    1 / 6 (16.67%)
         occurrences all number
    1
    5
    2
    1
    Rash
         subjects affected / exposed
    0 / 20 (0.00%)
    4 / 32 (12.50%)
    0 / 20 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    4
    0
    1
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    1 / 20 (5.00%)
    2 / 32 (6.25%)
    1 / 20 (5.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    2
    1
    0
    Pruritus
         subjects affected / exposed
    0 / 20 (0.00%)
    3 / 32 (9.38%)
    1 / 20 (5.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    5
    1
    0
    Alopecia
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 32 (6.25%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Rash macular
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 32 (6.25%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Skin hyperpigmentation
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 32 (3.13%)
    0 / 20 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    2
    0
    1
    Renal and urinary disorders
    Proteinuria
         subjects affected / exposed
    7 / 20 (35.00%)
    7 / 32 (21.88%)
    6 / 20 (30.00%)
    2 / 6 (33.33%)
         occurrences all number
    20
    15
    10
    4
    Haematuria
         subjects affected / exposed
    3 / 20 (15.00%)
    2 / 32 (6.25%)
    1 / 20 (5.00%)
    0 / 6 (0.00%)
         occurrences all number
    3
    4
    1
    0
    Acute kidney injury
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 32 (3.13%)
    2 / 20 (10.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    2
    0
    Urinary incontinence
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 32 (0.00%)
    2 / 20 (10.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    2 / 20 (10.00%)
    8 / 32 (25.00%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    4
    8
    0
    0
    Hyperthyroidism
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 32 (3.13%)
    0 / 20 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    0
    2
    Thyroid pain
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 32 (0.00%)
    0 / 20 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    5 / 20 (25.00%)
    9 / 32 (28.13%)
    4 / 20 (20.00%)
    1 / 6 (16.67%)
         occurrences all number
    6
    17
    8
    1
    Back pain
         subjects affected / exposed
    5 / 20 (25.00%)
    4 / 32 (12.50%)
    4 / 20 (20.00%)
    0 / 6 (0.00%)
         occurrences all number
    6
    7
    6
    0
    Musculoskeletal pain
         subjects affected / exposed
    1 / 20 (5.00%)
    3 / 32 (9.38%)
    1 / 20 (5.00%)
    0 / 6 (0.00%)
         occurrences all number
    2
    3
    1
    0
    Myalgia
         subjects affected / exposed
    2 / 20 (10.00%)
    1 / 32 (3.13%)
    2 / 20 (10.00%)
    0 / 6 (0.00%)
         occurrences all number
    3
    2
    4
    0
    Muscle spasms
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 32 (0.00%)
    4 / 20 (20.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    6
    0
    Pain in extremity
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 32 (0.00%)
    2 / 20 (10.00%)
    2 / 6 (33.33%)
         occurrences all number
    0
    0
    3
    2
    Flank pain
         subjects affected / exposed
    1 / 20 (5.00%)
    2 / 32 (6.25%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    4
    2
    0
    0
    Torticollis
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 32 (0.00%)
    2 / 20 (10.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    3
    0
    Infections and infestations
    COVID-19
         subjects affected / exposed
    3 / 20 (15.00%)
    11 / 32 (34.38%)
    0 / 20 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    3
    16
    0
    1
    Urinary tract infection
         subjects affected / exposed
    0 / 20 (0.00%)
    5 / 32 (15.63%)
    3 / 20 (15.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    5
    4
    0
    Nasopharyngitis
         subjects affected / exposed
    1 / 20 (5.00%)
    3 / 32 (9.38%)
    1 / 20 (5.00%)
    0 / 6 (0.00%)
         occurrences all number
    2
    3
    1
    0
    Influenza
         subjects affected / exposed
    1 / 20 (5.00%)
    2 / 32 (6.25%)
    0 / 20 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    2
    2
    0
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    5 / 20 (25.00%)
    6 / 32 (18.75%)
    7 / 20 (35.00%)
    0 / 6 (0.00%)
         occurrences all number
    7
    20
    14
    0
    Hyperkalaemia
         subjects affected / exposed
    1 / 20 (5.00%)
    3 / 32 (9.38%)
    2 / 20 (10.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    3
    2
    0
    Hypomagnesaemia
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 32 (0.00%)
    2 / 20 (10.00%)
    3 / 6 (50.00%)
         occurrences all number
    1
    0
    2
    3
    Hyperuricaemia
         subjects affected / exposed
    1 / 20 (5.00%)
    2 / 32 (6.25%)
    1 / 20 (5.00%)
    1 / 6 (16.67%)
         occurrences all number
    1
    3
    1
    1
    Hypertriglyceridaemia
         subjects affected / exposed
    0 / 20 (0.00%)
    3 / 32 (9.38%)
    0 / 20 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    9
    0
    1
    Hypocalcaemia
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 32 (3.13%)
    3 / 20 (15.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    3
    0
    Hypophosphataemia
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 32 (3.13%)
    2 / 20 (10.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    1
    2
    0
    Hypokalaemia
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 32 (0.00%)
    0 / 20 (0.00%)
    2 / 6 (33.33%)
         occurrences all number
    1
    0
    0
    4
    Hyponatraemia
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 32 (3.13%)
    0 / 20 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    1
    2
    0
    1
    Dehydration
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 32 (0.00%)
    0 / 20 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    07 Feb 2021
    Revision of eligibility criteria. Minor clarifications.
    23 Jun 2021
    Added clarifications per health authority request. Removed proton pump inhibitors from the list of prohibited therapies and instructions to avoid proton pump inhibitors. Clarified the screening pregnancy test was to be completed within 7 days before the start of surufatinib treatment. Removed C1D2 visit; added screening visit range Day -7 to 1. Added provision to allow enrollment of additional patients. Minor clarifications and modifications for consistency.
    12 Aug 2021
    Added clarifications about enrollment. Addressed Ethic Committee comments. Minor clarifications and addition of United States sites.
    01 Mar 2022
    Language was updated to reflect company name change and throughout the document for clarity. Updated total enrollment.
    05 Dec 2022
    Language updated for clarity throughout the document. The addition of the time window was intended to provide flexibility in obtaining patient assessments relative to dosing.

    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.
    Based upon the strategic reevaluation of the clinical development program for surufatinib in Europe and the US, the study was terminated. The termination was not based on any concern for patient safety or efficacy relative to surufatinib treatment.
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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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