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    Clinical Trial Results:
    Mesothelioma Stratified Therapy (MiST): A stratified multi-arm phase IIa clinical trial to enable accelerated evaluation of targeted therapies for relapsed malignant mesothelioma.

    Summary
    EudraCT number
    		 2017-003353-41
    Trial protocol
    		 GB  
    Global end of trial date
    18 Oct 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    18 Mar 2026
    First version publication date
    18 Mar 2026
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    0627
    Additional study identifiers
    ISRCTN number
    		 ISRCTN39816629
    US NCT number
    		 NCT03654833
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 NIHR Portfolio Adoption number: 38247
    Sponsors
    Sponsor organisation name
    University of Leicester
    Sponsor organisation address
    Research Governance Office, Research & Enterprise Office, University of Leicester, Leicester, United Kingdom,
    Public contact
    Professor Dean Fennell, University of Leicester, 0044 01162297249, df132@leicester.ac.uk
    Scientific contact
    Professor Dean Fennell, University of Leicester, 0044 01162297249, mistmailbox@leicester.ac.uk
    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
    19 Aug 2024
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    03 Apr 2024
    Global end of trial reached?
    Yes
    Global end of trial date
    18 Oct 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To determine the disease control rate of stratified targeted therapies in relapsed mesothelioma at 12 weeks MiST1 will evaluate the oral poly-ADP ribose polymerase (PARP) inhibitor rucaparib in patients with a specific molecular biomarker profile (loss of expression of BAP1 and/or BRCA1) MiST2 will evaluate the oral small molecule inhibitor of CDK4 and CDK6 abemaciclib in patients with a specific molecular biomarker profile (loss of expression of p16INK4A) MiST3 will evaluate the intravenously administered drug (pembrolizumab) in combination with the oral therapy (bemcentinib) in patients with no specific biomarker MiST4 will evaluate the intravenously administered drug combination atezolizumab and bevacizumab in patients with a specific molecular biomarker profile (positive for PDL1 expression) MiST5 will evaluate the intravenously administered drug (dostarlimab) in combination with the oral therapy (niraparib) in patients with Platinum Sensitive Relapsed Mesothelioma
    Protection of trial subjects
    In order to confidently ensure the safety of participants and ensure the confidence of the collaborating pharmaceutical companies, patients can only be treated at sites that have been assessed to confirm that they have the required facilities and experience to administer treatment safely.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    29 Jan 2019
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 130
    Worldwide total number of subjects
    130
    EEA total number of subjects
    0
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    33
    From 65 to 84 years
    95
    85 years and over
    2

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 186 patients were enrolled to MIST Master and 130 participants were recruited to arms. 26 participants were included in each MiST arm. An additional patient was recruited in MiST-5 and died before receiving treatment, they were therefore replaced with another participant and are not included in the figures reported here.

    Pre-assignment
    Screening details
    		 MiST-1: 36 screened, 10 were found ineligible. 26 entered the trial MiST-2: 30 screened, 4 were found ineligible. 26 entered the trial MiST-3: 41 screened, 15 were found ineligible. 26 entered the trial MiST-4: 30 screened, 4 were found ineligible. 26 entered the trial MiST-5: 29 screened, 2 were found ineligible, 27 entered the trial

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 MiST 1
    Arm description
    		 Trial Participants: Relapsed mesothelioma patients with prior treatment response to platinum doublet therapy. Investigational Medicinal Product: Rucaparib supplied by Clovis Oncology, Inc.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Rucaparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    600mg twice daily (BID) every 28 days

    Arm title
    		 MiST 2
    Arm description
    		 Trial Participants: Relapsed mesothelioma patients previously treated with platinum doublet therapy. Investigational Medicinal Product: Abemaciclib supplied by Lilly.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Abemaciclib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    200mg twice daily (BID) for 28 days

    Arm title
    		 MiST 3
    Arm description
    		 Trial Participants: Patients with relapsed mesothelioma previously treated with platinum doublet therapy. Investigational Medicinal Products: Bemcentinib will be supplied by BerGenBio. Pembrolizumab will be supplied by MSD.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Bemcentinib & Pembrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection, Capsule
    Routes of administration
    Intravenous use, Oral use
    Dosage and administration details
    Bemcentinib will be administered once daily. On the first 3 days of administration the dose will be a loading dose of 400mg. From Day 4 onwards, patients will receive a daily dose of 200mg. Each cycle will be 21 days duration. Pembrolizumab will be given at a fixed dose of 200mg via IV infusion on Day 1 of each 21-day cycle. Each drug will be administered for up to 35 cycles or until loss of clinical benefit, unacceptable toxicity or symptomatic deterioration attributed to disease progression.

    Arm title
    		 MiST 4
    Arm description
    		 Trial Participants: Relapsed mesothelioma patients previously treated with platinum doublet therapy. Investigational Medicinal Products: Atezolizumab and bevacizumab supplied by Roche/Genentech.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Atezolizumab and bevacizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Atezolizumab will be given as a fixed dose of 1200 milligrams (mg) via intravenous (IV) infusion on day 1 of a 21-day cycle. Bevacizumab will be given as 15 milligrams per kilogram (mg/kg) via IV infusion on Days 1 of a 21-day cycle.

    Arm title
    		 MiST 5
    Arm description
    		 Trial Participants: Patients who have had Response or Stable disease, but not progression as their best response to first line or re challenge platinum doublet therapy. Investigational Medicinal Products: Niraparib and dostarlimab supplied by GSK.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Niraparib and dostarlimab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, Infusion
    Routes of administration
    Oral use, Intravenous use
    Dosage and administration details
    Niraparib will be administered once daily depending on patient’s weight and platelet count. A cycle consist of 21 days and there will be up to 35 cycles in total: • ≥77 kg and ≥150,000 μL 300 mg (3 X 100 mg capsules) • <77 kg or <150,000 μL 200 mg (2 X 100 mg capsules) Dostarlimab will be given at a fixed dose of 500mg via IV infusion on Day 1 of each 21-day cycle for 4 cycles. Followed by 1000mg via IV infusion on Day 1 of each 42-day cycle for up to 24 months. • Each will be administered for up to 24 months or until loss of clinical benefit, unacceptable toxicity or symptomatic deterioration attributed to disease progression

    Number of subjects in period 1
    		MiST 1 MiST 2 MiST 3 MiST 4 MiST 5
    Started
    26
    26
    26
    26
    26
    Completed
    26
    26
    26
    26
    26
    Period 2
    Period 2 title
    12 Weeks
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 MiST 1
    Arm description
    		 Trial Participants: Relapsed mesothelioma patients with prior treatment response to platinum doublet therapy. Investigational Medicinal Products: Rucaparib supplied by Clovis Oncology, Inc.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Rucaparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    600mg twice daily (BID) every 28 days

    Arm title
    		 MiST 2
    Arm description
    		 Trial Participants: Relapsed mesothelioma patients previously treated with platinum doublet therapy. Investigational Medicinal Products: Abemaciclib supplied by Lilly.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Abemaciclib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    200mg twice daily (BID) for 28 days

    Arm title
    		 MiST 3
    Arm description
    		 Trial Participants: Patients with relapsed mesothelioma previously treated with platinum doublet therapy. Investigational Medicinal Products: Bemcentinib will be supplied by BerGenBio. Pembrolizumab will be supplied by MSD.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Bemcentinib & Pembrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, Injection
    Routes of administration
    Intravenous use, Oral use
    Dosage and administration details
    Bemcentinib will be administered once daily. On the first 3 days of administration the dose will be a loading dose of 400mg. From Day 4 onwards, patients will receive a daily dose of 200mg. Each cycle will be 21 days duration. Pembrolizumab will be given at a fixed dose of 200mg via IV infusion on Day 1 of each 21-day cycle. Each drug will be administered for up to 35 cycles or until loss of clinical benefit, unacceptable toxicity or symptomatic deterioration attributed to disease progression.

    Arm title
    		 MiST 4
    Arm description
    		 Trial Participants: Relapsed mesothelioma patients previously treated with platinum doublet therapy. Investigational Medicinal Products: Atezolizumab and bevacizumab supplied by Roche/Genentech.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Atezolizumab and bevacizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Atezolizumab will be given as a fixed dose of 1200 milligrams (mg) via intravenous (IV) infusion on day 1 of a 21-day cycle. Bevacizumab will be given as 15 milligrams per kilogram (mg/kg) via IV infusion on Days 1 of a 21-day cycle.

    Arm title
    		 MiST 5
    Arm description
    		 Trial Participants: Patients who have had Response or Stable disease, but not progression as their best response to first line or re challenge platinum doublet therapy. Investigational Medicinal Product: Niraparib and dostarlimab supplied by GSK.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Niraparib and dostarlimab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, Infusion
    Routes of administration
    Intravenous use, Oral use
    Dosage and administration details
    Niraparib will be administered once daily depending on patient’s weight and platelet count. A cycle consist of 21 days and there will be up to 35 cycles in total: • ≥77 kg and ≥150,000 μL 300 mg (3 X 100 mg capsules) • <77 kg or <150,000 μL 200 mg (2 X 100 mg capsules) Dostarlimab will be given at a fixed dose of 500mg via IV infusion on Day 1 of each 21-day cycle for 4 cycles. Followed by 1000mg via IV infusion on Day 1 of each 42-day cycle for up to 24 months. • Each will be administered for up to 24 months or until loss of clinical benefit, unacceptable toxicity or symptomatic deterioration attributed to disease progression

    Number of subjects in period 2
    		MiST 1 MiST 2 MiST 3 MiST 4 MiST 5
    Started
    26
    26
    26
    26
    26
    Completed
    18
    14
    18
    18
    21
    Not completed
    8
    12
    8
    8
    5
         Physician decision
    1
    2
    -
    -
    -
         Toxicity
    1
    1
    -
    -
    -
         Death
    -
    2
    3
    3
    -
         Patient Choice
    -
    1
    -
    -
    -
         Did not attend 12 week CT scan
    -
    -
    1
    -
    -
         Lack of efficacy
    6
    6
    4
    5
    5
    Period 3
    Period 3 title
    24 Weeks
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 MiST 1
    Arm description
    		 Trial Participants: Relapsed mesothelioma patients with prior treatment response to platinum doublet therapy. Investigational Medicinal Products: Rucaparib supplied by Clovis Oncology, Inc.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Rucaparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    600mg twice daily (BID) every 28 days

    Arm title
    		 MiST 2
    Arm description
    		 Trial Participants: Relapsed mesothelioma patients previously treated with platinum doublet therapy. Investigational Medicinal Products: Abemaciclib supplied by Lilly.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Abemaciclib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    200mg twice daily (BID) for 28 days

    Arm title
    		 MiST 3
    Arm description
    		 Trial Participants: Patients with relapsed mesothelioma previously treated with platinum doublet therapy. Investigational Medicinal Products: Bemcentinib will be supplied by BerGenBio. Pembrolizumab will be supplied by MSD.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Bemcentinib & Pembrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, Injection
    Routes of administration
    Intravenous use, Oral use
    Dosage and administration details
    Bemcentinib will be administered once daily. On the first 3 days of administration the dose will be a loading dose of 400mg. From Day 4 onwards, patients will receive a daily dose of 200mg. Each cycle will be 21 days duration. Pembrolizumab will be given at a fixed dose of 200mg via IV infusion on Day 1 of each 21-day cycle. Each drug will be administered for up to 35 cycles or until loss of clinical benefit, unacceptable toxicity or symptomatic deterioration attributed to disease progression.

    Arm title
    		 MiST 4
    Arm description
    		 Trial Participants: Relapsed mesothelioma patients previously treated with platinum doublet therapy. Investigational Medicinal Products: Atezolizumab and bevacizumab supplied by Roche/Genentech.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Atezolizumab and bevacizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Atezolizumab will be given as a fixed dose of 1200 milligrams (mg) via intravenous (IV) infusion on day 1 of a 21-day cycle. Bevacizumab will be given as 15 milligrams per kilogram (mg/kg) via IV infusion on Days 1 of a 21-day cycle.

    Arm title
    		 MiST 5
    Arm description
    		 Trial Participants: Patients who have had Response or Stable disease, but not progression as their best response to first line or re challenge platinum doublet therapy. Investigational Medicinal Products: Niraparib and dostarlimab supplied by GSK.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Niraparib and dostarlimab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, Infusion
    Routes of administration
    Intravenous use, Oral use
    Dosage and administration details
    Niraparib will be administered once daily depending on patient’s weight and platelet count. A cycle consist of 21 days and there will be up to 35 cycles in total: • ≥77 kg and ≥150,000 μL 300 mg (3 X 100 mg capsules) • <77 kg or <150,000 μL 200 mg (2 X 100 mg capsules) Dostarlimab will be given at a fixed dose of 500mg via IV infusion on Day 1 of each 21-day cycle for 4 cycles. Followed by 1000mg via IV infusion on Day 1 of each 42-day cycle for up to 24 months. • Each will be administered for up to 24 months or until loss of clinical benefit, unacceptable toxicity or symptomatic deterioration attributed to disease progression

    Number of subjects in period 3
    		MiST 1 MiST 2 MiST 3 MiST 4 MiST 5
    Started
    18
    14
    18
    18
    21
    Completed
    10
    7
    10
    9
    11
    Not completed
    8
    7
    8
    9
    10
         Physician decision
    -
    -
    -
    -
    1
         Missed 24 week visit
    -
    1
    -
    -
    -
         Death
    -
    1
    4
    1
    3
         Patient Choice
    -
    1
    -
    -
    -
         Lack of efficacy
    8
    4
    4
    8
    6

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    MiST 1
    Reporting group description
    		 Trial Participants: Relapsed mesothelioma patients with prior treatment response to platinum doublet therapy. Investigational Medicinal Product: Rucaparib supplied by Clovis Oncology, Inc.

    Reporting group title
    MiST 2
    Reporting group description
    		 Trial Participants: Relapsed mesothelioma patients previously treated with platinum doublet therapy. Investigational Medicinal Product: Abemaciclib supplied by Lilly.

    Reporting group title
    MiST 3
    Reporting group description
    		 Trial Participants: Patients with relapsed mesothelioma previously treated with platinum doublet therapy. Investigational Medicinal Products: Bemcentinib will be supplied by BerGenBio. Pembrolizumab will be supplied by MSD.

    Reporting group title
    MiST 4
    Reporting group description
    		 Trial Participants: Relapsed mesothelioma patients previously treated with platinum doublet therapy. Investigational Medicinal Products: Atezolizumab and bevacizumab supplied by Roche/Genentech.

    Reporting group title
    MiST 5
    Reporting group description
    		 Trial Participants: Patients who have had Response or Stable disease, but not progression as their best response to first line or re challenge platinum doublet therapy. Investigational Medicinal Products: Niraparib and dostarlimab supplied by GSK.

    Reporting group values
    		 MiST 1 MiST 2 MiST 3 MiST 4 MiST 5 Total
    Number of subjects
    		 26 26 26 26 26 130
    Age categorical
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 12 8 3 6 4 33
        From 65-84 years
    		 14 18 22 20 21 95
        85 years and over
    		 0 0 1 0 1 2
    Age continuous
    Age continuous
    Units: years
        median (inter-quartile range (Q1-Q3))
    		 66.5 (60.0 to 71.0) 67.5 (64.0 to 74.0) 72.5 (69.0 to 75.0) 68 (67.0 to 74.0) 69.5 (68.0 to 74.0) -
    Gender categorical
    Gender
    Units: Subjects
        Female
    		 4 3 3 8 5 23
        Male
    		 22 23 23 18 21 107
    Smoking status
    Smoking status
    Units: Subjects
        Smoker
    		 2 2 1 2 4 11
        Non smoker
    		 15 14 12 13 12 66
        Ex smoker
    		 9 10 13 11 10 53
    Mesothelioma subtype
    Mesothelioma subtype
    Units: Subjects
        Epithelioid
    		 21 21 23 20 21 106
        Biphasic
    		 5 4 2 2 1 14
        Sarcomatoid
    		 0 0 1 3 2 6
        NOS
    		 0 1 0 1 2 4
    History of asbestos
    History of asbestos
    Units: Subjects
        Yes
    		 15 20 20 16 18 89
        No
    		 2 2 0 2 0 6
        Unknown
    		 9 4 6 8 8 35
    ECOG status
    ECOG status
    Units: Subjects
        zero
    		 4 4 6 4 2 20
        one
    		 22 22 20 22 24 110
    Primary Tumour Site
    Primary Tumour Site
    Units: Subjects
        Thoracic
    		 25 26 25 24 24 124
        Abdominal
    		 1 0 0 1 2 4
        Pelvis
    		 0 0 0 1 0 1
        Missing
    		 0 0 1 0 0 1
    T-stage
    T-stage
    Units: Subjects
        T1
    		 3 4 5 2 6 20
        T2
    		 3 9 2 3 4 21
        T3
    		 10 5 9 7 6 37
        T4
    		 9 8 6 13 8 44
        TX
    		 0 0 2 1 0 3
        Unobtainable
    		 0 0 2 0 1 3
        Missing
    		 1 0 0 0 1 2
    N-stage
    N-stage
    Units: Subjects
        N0
    		 9 10 16 11 13 59
        N1
    		 6 8 6 6 7 33
        N2
    		 7 8 2 8 2 27
        N3
    		 3 0 0 1 2 6
        Unobtainable
    		 0 0 2 0 1 3
        Missing
    		 1 0 0 0 1 2
    M-stage
    M-stage
    Units: Subjects
        M0
    		 21 21 19 20 16 97
        M1
    		 4 5 5 6 6 26
        Unobtainable
    		 0 0 2 0 3 5
        Missing
    		 1 0 0 0 1 2
    P16 negative
    P16 negative
    Units: Subjects
        Positive
    		 6 0 0 7 0 13
        Negative
    		 20 26 0 10 0 56
        Not applicable
    		 0 0 26 9 26 61
    Number of prior courses of systemic anticancer therapy
    Number of prior courses of systemic anticancer therapy
    Units: Subjects
        One
    		 12 10 17 12 20 71
        Two
    		 6 7 7 8 6 34
        Three
    		 6 5 2 4 0 17
        Four
    		 1 3 0 1 0 5
        Five
    		 1 1 0 1 0 3
    First line therapy
    First line therapy
    Units: Subjects
        Bevacizumab and Pemetrexed and/or Carboplatin
    		 0 0 5 0 1 6
        Bevacizumab alone
    		 0 0 0 0 1 1
        Pemetrexed alone
    		 0 0 0 0 1 1
        Pemetrexed and/or Carboplatin
    		 0 17 11 16 17 61
        Pemetrexed and/or Cisplatin
    		 0 8 8 5 3 24
        Radiotherapy
    		 0 1 1 0 0 2
        Pemetrexed and Cisplatin/Carboplatin
    		 0 0 1 0 0 1
        Pemetrexed/Carboplatin
    		 7 0 0 0 0 7
        Pemetrexed/Cisplatin
    		 3 0 0 0 0 3
        Pemetrexed & Carboplatin
    		 9 0 0 0 0 9
        Pemetrexed & Cisplatin
    		 3 0 0 0 0 3
        Pemetrexed & Cisplatin & Bevacizumab
    		 1 0 0 0 0 1
        Other
    		 3 0 0 5 0 8
        Missing
    		 0 0 0 0 3 3
    Second line therapy
    Second line therapy
    Units: Subjects
        Pemetrexed and/or Carboplatin
    		 4 5 3 3 2 17
        Bevacizumab
    		 2 0 2 0 1 5
        ADI-Peg 20/placebo
    		 0 0 0 0 1 1
        RSO-1
    		 0 0 0 0 1 1
        Carboplatin and taxel
    		 0 0 0 0 1 1
        Pemetrexed and/or Cisplatin
    		 0 1 0 3 0 4
        Vinorelbine
    		 0 2 0 4 0 6
        Gemcitabine & AZD6738
    		 0 0 1 0 0 1
        Pemetrexed/Carboplatin and Bevicizumab
    		 0 0 1 0 0 1
        Vinorelbine & carboplatin
    		 0 0 1 0 0 1
        Radiotherapy
    		 0 0 1 0 0 1
        Rucaparib
    		 0 2 0 0 0 2
        Nivolumab/Placebo
    		 0 4 0 0 0 4
        Other
    		 6 2 0 0 0 8
        Pembrollizumab + Defactinib
    		 1 0 0 0 0 1
        Missing
    		 13 10 17 16 20 76
    Body Mass Index
    Body Mass Index
    Units: kg/m^2
        median (inter-quartile range (Q1-Q3))
    		 26.0 (23.7 to 29.3) 25.5 (24.0 to 28.5) 26.6 (23.4 to 28.9) 25.7 (21.9 to 28.8) 25.5 (24.1 to 28.0) -

    End points

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    End points reporting groups
    Reporting group title
    MiST 1
    Reporting group description
    		 Trial Participants: Relapsed mesothelioma patients with prior treatment response to platinum doublet therapy. Investigational Medicinal Product: Rucaparib supplied by Clovis Oncology, Inc.

    Reporting group title
    MiST 2
    Reporting group description
    		 Trial Participants: Relapsed mesothelioma patients previously treated with platinum doublet therapy. Investigational Medicinal Product: Abemaciclib supplied by Lilly.

    Reporting group title
    MiST 3
    Reporting group description
    		 Trial Participants: Patients with relapsed mesothelioma previously treated with platinum doublet therapy. Investigational Medicinal Products: Bemcentinib will be supplied by BerGenBio. Pembrolizumab will be supplied by MSD.

    Reporting group title
    MiST 4
    Reporting group description
    		 Trial Participants: Relapsed mesothelioma patients previously treated with platinum doublet therapy. Investigational Medicinal Products: Atezolizumab and bevacizumab supplied by Roche/Genentech.

    Reporting group title
    MiST 5
    Reporting group description
    		 Trial Participants: Patients who have had Response or Stable disease, but not progression as their best response to first line or re challenge platinum doublet therapy. Investigational Medicinal Products: Niraparib and dostarlimab supplied by GSK.
    Reporting group title
    MiST 1
    Reporting group description
    		 Trial Participants: Relapsed mesothelioma patients with prior treatment response to platinum doublet therapy. Investigational Medicinal Products: Rucaparib supplied by Clovis Oncology, Inc.

    Reporting group title
    MiST 2
    Reporting group description
    		 Trial Participants: Relapsed mesothelioma patients previously treated with platinum doublet therapy. Investigational Medicinal Products: Abemaciclib supplied by Lilly.

    Reporting group title
    MiST 3
    Reporting group description
    		 Trial Participants: Patients with relapsed mesothelioma previously treated with platinum doublet therapy. Investigational Medicinal Products: Bemcentinib will be supplied by BerGenBio. Pembrolizumab will be supplied by MSD.

    Reporting group title
    MiST 4
    Reporting group description
    		 Trial Participants: Relapsed mesothelioma patients previously treated with platinum doublet therapy. Investigational Medicinal Products: Atezolizumab and bevacizumab supplied by Roche/Genentech.

    Reporting group title
    MiST 5
    Reporting group description
    		 Trial Participants: Patients who have had Response or Stable disease, but not progression as their best response to first line or re challenge platinum doublet therapy. Investigational Medicinal Product: Niraparib and dostarlimab supplied by GSK.
    Reporting group title
    MiST 1
    Reporting group description
    		 Trial Participants: Relapsed mesothelioma patients with prior treatment response to platinum doublet therapy. Investigational Medicinal Products: Rucaparib supplied by Clovis Oncology, Inc.

    Reporting group title
    MiST 2
    Reporting group description
    		 Trial Participants: Relapsed mesothelioma patients previously treated with platinum doublet therapy. Investigational Medicinal Products: Abemaciclib supplied by Lilly.

    Reporting group title
    MiST 3
    Reporting group description
    		 Trial Participants: Patients with relapsed mesothelioma previously treated with platinum doublet therapy. Investigational Medicinal Products: Bemcentinib will be supplied by BerGenBio. Pembrolizumab will be supplied by MSD.

    Reporting group title
    MiST 4
    Reporting group description
    		 Trial Participants: Relapsed mesothelioma patients previously treated with platinum doublet therapy. Investigational Medicinal Products: Atezolizumab and bevacizumab supplied by Roche/Genentech.

    Reporting group title
    MiST 5
    Reporting group description
    		 Trial Participants: Patients who have had Response or Stable disease, but not progression as their best response to first line or re challenge platinum doublet therapy. Investigational Medicinal Products: Niraparib and dostarlimab supplied by GSK.

    Subject analysis set title
    Dummy analysis
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    A placeholder value of 1 was entered for [Dummy Arm Name] to satisfy system validation requirements for a single-arm sub-study. This arm does not exist in the clinical protocol, and no data from this 'subject' was used in the actual analysis.

    Primary: Disease Control Rate at 12 weeks

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    End point title
    		 Disease Control Rate at 12 weeks
    End point description
    End point type
    Primary
    End point timeframe
    12 week
    End point values
    		 MiST 1 MiST 2 MiST 3 MiST 4 MiST 5 Dummy analysis
    Number of subjects analysed
    26
    26
    26
    26
    26
    1 [1]
    Units: Number of patients
        Complete Response
    0
    0
    0
    0
    0
    0
        Partial Response
    2
    3
    4
    1
    3
    0
        Stable Disease
    13
    11
    8
    12
    14
    0
        Progressive Disease
    10
    2
    11
    8
    8
    0
        Not Evaluable
    1
    10
    3
    5
    1
    1
    Notes
    [1] - Placeholder value of 1 was entered for Dummy Arm to satisfy system validation requirements
    Statistical analysis title
    		 MiST 1 Disease Control Rate at 12 weeks
    Statistical analysis description
    The primary analysis of the primary outcome, DCR12w, will be analysed in the efficacy population. Patients will be included in the analysis if they have received at least one dose of study treatment. A total of 26 evaluable patients will be analysed for this arm. Proportion of patients with DCR will be presented with exact 95% confidence intervals.
    Comparison groups
    MiST 1 v Dummy analysis
    Number of subjects included in analysis
    27
    Analysis specification
    Pre-specified
    Analysis type
    		 other [2]
    Method
    Parameter type
    		 Proportion
    Point estimate
    57.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 36.9
         upper limit
    		 76.7
    Notes
    [2] - Comparison of a proportion to a reference value. Disease control in at least 11/26 patients, will result in the rejecting of the null hypothesis and concluding that the true response rate is greater than 25%. In this case the null hypothesis was rejected.
    Statistical analysis title
    		 MiST 2 Disease Control Rate at 12 weeks
    Statistical analysis description
    The primary analysis of the primary outcome, DCR12w, will be analysed in the efficacy population. Patients will be included in the analysis if they have received at least one dose of study treatment. A total of 26 evaluable patients will be analysed for this arm. Proportion of patients with DCR will be presented with exact 90% confidence intervals.
    Comparison groups
    MiST 2 v Dummy analysis
    Number of subjects included in analysis
    27
    Analysis specification
    Pre-specified
    Analysis type
    		 other [3]
    Method
    Parameter type
    		 Proportion
    Point estimate
    53.8
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 36.2
         upper limit
    		 70.8
    Notes
    [3] - Comparison of a proportion to a reference value. Disease control in at least 11/26 patients, will result in the rejecting of the null hypothesis and concluding that the true response rate is greater than 25%. In this case the null hypothesis was rejected.
    Statistical analysis title
    		 MiST 3 Disease Control Rate at 12 weeks
    Statistical analysis description
    The primary analysis of the primary outcome, DCR12w, will be analysed in the efficacy population. Patients will be included in the analysis if they have received at least one dose of study treatment. A total of 26 evaluable patients will be analysed for this arm. Proportion of patients with DCR will be presented with exact 90% confidence intervals.
    Comparison groups
    MiST 3 v Dummy analysis
    Number of subjects included in analysis
    27
    Analysis specification
    Pre-specified
    Analysis type
    		 other [4]
    Method
    Parameter type
    		 Proportion
    Point estimate
    46.2
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 29.2
         upper limit
    		 63.8
    Notes
    [4] - Comparison of a proportion to a reference value. Disease control in at least 11/26 patients, will result in the rejecting of the null hypothesis and concluding that the true response rate is greater than 25%. In this case the null hypothesis was rejected.
    Statistical analysis title
    		 MiST 4 Disease Control Rate at 12 weeks
    Statistical analysis description
    The primary analysis of the primary outcome, DCR12w, will be analysed in the efficacy population. Patients will be included in the analysis if they have received at least one dose of study treatment. A total of 26 evaluable patients will be analysed for this arm. Proportion of patients with DCR will be presented with exact 90% confidence intervals.
    Comparison groups
    MiST 4 v Dummy analysis
    Number of subjects included in analysis
    27
    Analysis specification
    Pre-specified
    Analysis type
    		 other [5]
    Method
    Parameter type
    		 Proportion
    Point estimate
    50
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 32.7
         upper limit
    		 67.3
    Notes
    [5] - Comparison of a proportion to a reference value. Disease control in at least 11/26 patients, will result in the rejecting of the null hypothesis and concluding that the true response rate is greater than 25%. In this case the null hypothesis was rejected.
    Statistical analysis title
    		 MiST 5 Disease Control Rate at 12 weeks
    Statistical analysis description
    The primary analysis of the primary outcome, DCR12w, will be analysed in the efficacy population. Patients will be included in the analysis if they have received at least one dose of study treatment. A total of 26 evaluable patients will be analysed for this arm. Proportion of patients with DCR will be presented with exact 90% confidence intervals.
    Comparison groups
    MiST 5 v Dummy analysis
    Number of subjects included in analysis
    27
    Analysis specification
    Pre-specified
    Analysis type
    		 other [6]
    Method
    Parameter type
    		 Proportion
    Point estimate
    65.4
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 47.4
         upper limit
    		 80.6
    Notes
    [6] - Comparison of a proportion to a reference value. Disease control in at least 11/26 patients, will result in the rejecting of the null hypothesis and concluding that the true response rate is greater than 25%. In this case the null hypothesis was rejected.

    Secondary: Objective Response Rate at 24 weeks

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    End point title
    		 Objective Response Rate at 24 weeks
    End point description
    End point type
    Secondary
    End point timeframe
    24 weeks
    End point values
    		 MiST 1 MiST 2 MiST 3 MiST 4 MiST 5 Dummy analysis
    Number of subjects analysed
    26
    26
    26
    26
    26
    1 [7]
    Units: Number of patients
        Complete Response
    0
    0
    0
    0
    0
    0
        Partial Response
    3
    4
    4
    1
    4
    0
        Stable Disease
    16
    14
    15
    18
    17
    0
        Progressive Disease
    4
    2
    5
    4
    4
    0
        Not Evaluable
    3
    6
    2
    3
    1
    1
    Notes
    [7] - Placeholder value of 1 was entered for Dummy Arm to satisfy system validation requirements
    Statistical analysis title
    		 MiST 1 Objective Response Rate at 24 weeks
    Statistical analysis description
    The secondary analysis of the secondary outcome, ORR24w, will be analysed in the efficacy population. Patients will be included in the analysis if they have received at least one dose of study treatment. A total of 26 evaluable patients will be analysed for this arm. Proportion of patients with ORR will be presented with exact 95% confidence intervals.
    Comparison groups
    MiST 1 v Dummy analysis
    Number of subjects included in analysis
    27
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Proportion
    Point estimate
    11.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.5
         upper limit
    		 30.2
    Statistical analysis title
    		 MiST 2 Objective Response Rate at 24 weeks
    Statistical analysis description
    The secondary analysis of the secondary outcome, ORR24w, will be analysed in the efficacy population. Patients will be included in the analysis if they have received at least one dose of study treatment. A total of 26 evaluable patients will be analysed for this arm. Proportion of patients with ORR will be presented with exact 95% confidence intervals.
    Comparison groups
    MiST 2 v Dummy analysis
    Number of subjects included in analysis
    27
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Proportion
    Point estimate
    15.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.4
         upper limit
    		 34.9
    Statistical analysis title
    		 MiST 3 Objective Response Rate at 24 weeks
    Statistical analysis description
    The secondary analysis of the secondary outcome, ORR24w, will be analysed in the efficacy population. Patients will be included in the analysis if they have received at least one dose of study treatment. A total of 26 evaluable patients will be analysed for this arm. Proportion of patients with ORR will be presented with exact 95% confidence intervals.
    Comparison groups
    MiST 3 v Dummy analysis
    Number of subjects included in analysis
    27
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Proportion
    Point estimate
    15.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.4
         upper limit
    		 34.9
    Statistical analysis title
    		 MiST 4 Objective Response Rate at 24 weeks
    Statistical analysis description
    The secondary analysis of the secondary outcome, ORR24w, will be analysed in the efficacy population. Patients will be included in the analysis if they have received at least one dose of study treatment. A total of 26 evaluable patients will be analysed for this arm. Proportion of patients with ORR will be presented with exact 95% confidence intervals.
    Comparison groups
    MiST 4 v Dummy analysis
    Number of subjects included in analysis
    27
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Proportion
    Point estimate
    3.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.1
         upper limit
    		 19.6
    Statistical analysis title
    		 MiST 5 Objective Response Rate at 24 weeks
    Statistical analysis description
    The secondary analysis of the secondary outcome, ORR24w, will be analysed in the efficacy population. Patients will be included in the analysis if they have received at least one dose of study treatment. A total of 26 evaluable patients will be analysed for this arm. Proportion of patients with ORR will be presented with exact 95% confidence intervals.
    Comparison groups
    MiST 5 v Dummy analysis
    Number of subjects included in analysis
    27
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Proportion
    Point estimate
    15.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.4
         upper limit
    		 34.9

    Secondary: Disease Control Rate at 24 weeks

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    End point title
    		 Disease Control Rate at 24 weeks
    End point description
    End point type
    Secondary
    End point timeframe
    24 weeks
    End point values
    		 MiST 1 MiST 2 MiST 3 MiST 4 MiST 5 Dummy analysis
    Number of subjects analysed
    26
    26
    26
    26
    26
    1 [8]
    Units: Number of patients
        Complete Response
    0
    0
    0
    0
    0
    0
        Partial Response
    1
    3
    4
    0
    3
    0
        Stable Disease
    5
    3
    6
    7
    5
    0
        Progressive Disease
    19
    7
    12
    14
    17
    0
        Not Evaluable
    1
    13
    4
    5
    1
    1
    Notes
    [8] - Placeholder value of 1 was entered for Dummy Arm to satisfy system validation requirements
    Statistical analysis title
    		 MiST 1 Disease Control Rate at 24 weeks
    Statistical analysis description
    The primary analysis of the primary outcome, DCR24w, will be analysed in the efficacy population. Patients will be included in the analysis if they have received at least one dose of study treatment. A total of 26 evaluable patients will be analysed for this arm. Proportion of patients with DCR will be presented with exact 95% confidence intervals.
    Comparison groups
    MiST 1 v Dummy analysis
    Number of subjects included in analysis
    27
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Proportion
    Point estimate
    23.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 9
         upper limit
    		 43.7
    Statistical analysis title
    		 MiST 2 Disease Control Rate at 24 weeks
    Statistical analysis description
    The primary analysis of the primary outcome, DCR24w, will be analysed in the efficacy population. Patients will be included in the analysis if they have received at least one dose of study treatment. A total of 26 evaluable patients will be analysed for this arm. Proportion of patients with DCR will be presented with exact 95% confidence intervals.
    Comparison groups
    MiST 2 v Dummy analysis
    Number of subjects included in analysis
    27
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Proportion
    Point estimate
    23.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 9
         upper limit
    		 43.6
    Statistical analysis title
    		 MiST 3 Disease Control Rate at 24 weeks
    Statistical analysis description
    The primary analysis of the primary outcome, DCR24w, will be analysed in the efficacy population. Patients will be included in the analysis if they have received at least one dose of study treatment. A total of 26 evaluable patients will be analysed for this arm. Proportion of patients with DCR will be presented with exact 95% confidence intervals.
    Comparison groups
    MiST 3 v Dummy analysis
    Number of subjects included in analysis
    27
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Proportion
    Point estimate
    38.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 20.2
         upper limit
    		 59.4
    Statistical analysis title
    		 MiST 4 Disease Control Rate at 24 weeks
    Statistical analysis description
    The primary analysis of the primary outcome, DCR24w, will be analysed in the efficacy population. Patients will be included in the analysis if they have received at least one dose of study treatment. A total of 26 evaluable patients will be analysed for this arm. Proportion of patients with DCR will be presented with exact 95% confidence intervals.
    Comparison groups
    MiST 4 v Dummy analysis
    Number of subjects included in analysis
    27
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Proportion
    Point estimate
    26.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 11.6
         upper limit
    		 47.8
    Statistical analysis title
    		 MiST 5 Disease Control Rate at 24 weeks
    Statistical analysis description
    The primary analysis of the primary outcome, DCR24w, will be analysed in the efficacy population. Patients will be included in the analysis if they have received at least one dose of study treatment. A total of 26 evaluable patients will be analysed for this arm. Proportion of patients with DCR will be presented with exact 95% confidence intervals.
    Comparison groups
    MiST 5 v Dummy analysis
    Number of subjects included in analysis
    27
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Proportion
    Point estimate
    30.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 14.3
         upper limit
    		 51.8

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All adverse events in the database at time of data lock for primary outcome analysis.
    Adverse event reporting additional description
    In addition to the SAEs reported for MiST 1-5 participants, one individual that was pre screening for MiST-2 but did not go into the MiST-2 trial had a SAE. The SAE term: Dyspnea in SOC: Respiratory, thoracic and mediastinal disorders.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    28.1
    Reporting groups
    Reporting group title
    MiST 1
    Reporting group description
    		 -

    Reporting group title
    MiST 2
    Reporting group description
    		 -

    Reporting group title
    MiST 3
    Reporting group description
    		 -

    Reporting group title
    MiST 4
    Reporting group description
    		 -

    Reporting group title
    MiST 5
    Reporting group description
    		 -

    Serious adverse events
    		 MiST 1 MiST 2 MiST 3 MiST 4 MiST 5
    Total subjects affected by serious adverse events
         subjects affected / exposed
    9 / 26 (34.62%)
    6 / 26 (23.08%)
    10 / 26 (38.46%)
    11 / 26 (42.31%)
    9 / 26 (34.62%)
         number of deaths (all causes)
    12
    12
    16
    7
    15
         number of deaths resulting from adverse events
    0
    1
    0
    1
    1
    Vascular disorders
    Superior vena cava occlusion
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Peripheral swelling
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    2 / 26 (7.69%)
    0 / 26 (0.00%)
    2 / 26 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Pneumonitis
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Blood bilirubin increased
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Joint dislocation
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervical vertebral fracture
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Pericardial effusion
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Ischaemic stroke
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Thrombocytopenia
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterovesical fistula
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Autoimmune hepatitis
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatitis
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bone pain
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    2 / 26 (7.69%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    2 / 26 (7.69%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenic sepsis
         subjects affected / exposed
    2 / 26 (7.69%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 26 (3.85%)
    2 / 26 (7.69%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    2 / 26 (7.69%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Empyema
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    2 / 26 (7.69%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    Urinary tract infection
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Encephalitis
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 MiST 1 MiST 2 MiST 3 MiST 4 MiST 5
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    24 / 26 (92.31%)
    22 / 26 (84.62%)
    24 / 26 (92.31%)
    25 / 26 (96.15%)
    26 / 26 (100.00%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    2 / 26 (7.69%)
         occurrences all number
    0
    1
    0
    1
    2
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    14 / 26 (53.85%)
    16 / 26 (61.54%)
    12 / 26 (46.15%)
    8 / 26 (30.77%)
    12 / 26 (46.15%)
         occurrences all number
    14
    17
    16
    10
    12
    Dry mouth
         subjects affected / exposed
    3 / 26 (11.54%)
    1 / 26 (3.85%)
    2 / 26 (7.69%)
    1 / 26 (3.85%)
    2 / 26 (7.69%)
         occurrences all number
    3
    1
    2
    1
    2
    Mouth ulceration
         subjects affected / exposed
    2 / 26 (7.69%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    2
    0
    0
    1
    0
    Non cardiac chest pain
         subjects affected / exposed
    0 / 26 (0.00%)
    2 / 26 (7.69%)
    1 / 26 (3.85%)
    1 / 26 (3.85%)
    1 / 26 (3.85%)
         occurrences all number
    0
    2
    1
    2
    1
    Weight decreased
         subjects affected / exposed
    1 / 26 (3.85%)
    6 / 26 (23.08%)
    2 / 26 (7.69%)
    3 / 26 (11.54%)
    0 / 26 (0.00%)
         occurrences all number
    1
    6
    3
    4
    0
    Sore mouth or throat
         subjects affected / exposed
    1 / 26 (3.85%)
    3 / 26 (11.54%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    3 / 26 (11.54%)
         occurrences all number
    1
    3
    0
    0
    4
    Cold symptoms
         subjects affected / exposed
    0 / 26 (0.00%)
    2 / 26 (7.69%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    Fever
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 26 (3.85%)
    2 / 26 (7.69%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    1
    1
    2
    0
    0
    General pain
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    2 / 26 (7.69%)
    1 / 26 (3.85%)
    4 / 26 (15.38%)
         occurrences all number
    0
    1
    2
    1
    4
    Swollen legs and feet
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    3 / 26 (11.54%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    0
    0
    3
    0
    0
    Abdominal pain
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    2 / 26 (7.69%)
    0 / 26 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    Joint pain (Shoulder, hip and/or general)
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    2 / 26 (7.69%)
    0 / 26 (0.00%)
         occurrences all number
    0
    0
    0
    3
    0
    Nausea
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    2 / 26 (7.69%)
         occurrences all number
    0
    0
    0
    1
    2
    Decreased appetite
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    5 / 26 (19.23%)
         occurrences all number
    0
    0
    0
    1
    5
    Dizziness
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    0
    0
    0
    2
    Cough
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    3 / 26 (11.54%)
         occurrences all number
    0
    0
    0
    0
    3
    Neck or shoulder ache
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    0
    0
    0
    3
    Chest infection
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    3 / 26 (11.54%)
         occurrences all number
    0
    0
    0
    0
    3
    Lethargy
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    0
    0
    0
    2
    Restless legs syndrome
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    0
    0
    0
    2
    Increased sweating
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    0
    0
    0
    2
    Breathlessness
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    4 / 26 (15.38%)
         occurrences all number
    0
    0
    0
    0
    4
    COVID-19
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    0
    0
    0
    2
    Chills
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    0
    1
    0
    2
    Constipation
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    2 / 26 (7.69%)
    0 / 26 (0.00%)
         occurrences all number
    0
    0
    0
    3
    0
    Epistaxis
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    2 / 26 (7.69%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    0
    3
    1
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    8 / 26 (30.77%)
    6 / 26 (23.08%)
    3 / 26 (11.54%)
    1 / 26 (3.85%)
    5 / 26 (19.23%)
         occurrences all number
    9
    7
    3
    1
    5
    Shortness of breath
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    3 / 26 (11.54%)
    1 / 26 (3.85%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    3
    1
    1
    Cough
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    1
    0
    1
    0
    2
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    1
    0
    1
    0
    2
    Investigations
    Thrombocytopenia
         subjects affected / exposed
    0 / 26 (0.00%)
    3 / 26 (11.54%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    0
    3
    0
    0
    0
    Raised creatinine
         subjects affected / exposed
    0 / 26 (0.00%)
    4 / 26 (15.38%)
    4 / 26 (15.38%)
    2 / 26 (7.69%)
    0 / 26 (0.00%)
         occurrences all number
    0
    5
    4
    3
    0
    Weight loss
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    2 / 26 (7.69%)
    2 / 26 (7.69%)
    0 / 26 (0.00%)
         occurrences all number
    0
    1
    4
    2
    0
    Increased ALT
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    2 / 26 (7.69%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    0
    1
    4
    1
    0
    Increased AST
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    1 / 26 (3.85%)
    2 / 26 (7.69%)
    0 / 26 (0.00%)
         occurrences all number
    0
    1
    1
    2
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    3 / 26 (11.54%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    2 / 26 (7.69%)
    0 / 26 (0.00%)
         occurrences all number
    3
    1
    0
    3
    0
    Headache
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 26 (3.85%)
    1 / 26 (3.85%)
    4 / 26 (15.38%)
    0 / 26 (0.00%)
         occurrences all number
    1
    1
    1
    4
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    6 / 26 (23.08%)
    8 / 26 (30.77%)
    5 / 26 (19.23%)
    2 / 26 (7.69%)
    5 / 26 (19.23%)
         occurrences all number
    9
    14
    12
    2
    6
    Platelet count decreased
         subjects affected / exposed
    2 / 26 (7.69%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    2
    0
    0
    0
    2
    Neutropenia
         subjects affected / exposed
    1 / 26 (3.85%)
    4 / 26 (15.38%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    1
    8
    1
    0
    0
    Thrombocytopenia
         subjects affected / exposed
    0 / 26 (0.00%)
    2 / 26 (7.69%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    2
    0
    0
    2
    Ascites
         subjects affected / exposed
    0 / 26 (0.00%)
    2 / 26 (7.69%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    Leg and/or ankle oedema
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    2 / 26 (7.69%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    Hypomagnesaemia
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    2 / 26 (7.69%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    2 / 26 (7.69%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    Constipation
         subjects affected / exposed
    6 / 26 (23.08%)
    6 / 26 (23.08%)
    7 / 26 (26.92%)
    4 / 26 (15.38%)
    7 / 26 (26.92%)
         occurrences all number
    6
    6
    9
    4
    7
    Diarrhoea
         subjects affected / exposed
    7 / 26 (26.92%)
    13 / 26 (50.00%)
    7 / 26 (26.92%)
    2 / 26 (7.69%)
    1 / 26 (3.85%)
         occurrences all number
    9
    19
    12
    3
    2
    Nausea
         subjects affected / exposed
    18 / 26 (69.23%)
    9 / 26 (34.62%)
    11 / 26 (42.31%)
    1 / 26 (3.85%)
    9 / 26 (34.62%)
         occurrences all number
    21
    11
    12
    1
    10
    Vomiting
         subjects affected / exposed
    4 / 26 (15.38%)
    5 / 26 (19.23%)
    2 / 26 (7.69%)
    3 / 26 (11.54%)
    3 / 26 (11.54%)
         occurrences all number
    4
    7
    2
    3
    3
    Acid reflux
         subjects affected / exposed
    2 / 26 (7.69%)
    2 / 26 (7.69%)
    2 / 26 (7.69%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    2
    2
    2
    0
    0
    Abdominal pain
         subjects affected / exposed
    1 / 26 (3.85%)
    2 / 26 (7.69%)
    2 / 26 (7.69%)
    1 / 26 (3.85%)
    4 / 26 (15.38%)
         occurrences all number
    1
    3
    2
    1
    4
    Dysphagia
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 26 (3.85%)
    2 / 26 (7.69%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    1
    1
    3
    0
    1
    Oral candidiasis
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    2 / 26 (7.69%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    Mucositis
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    2 / 26 (7.69%)
    2 / 26 (7.69%)
         occurrences all number
    0
    0
    1
    2
    2
    Hepatobiliary disorders
    Increased ALT
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    2 / 26 (7.69%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    Increased AST
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    3 / 26 (11.54%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    0
    0
    3
    0
    0
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    3 / 26 (11.54%)
    3 / 26 (11.54%)
    4 / 26 (15.38%)
    4 / 26 (15.38%)
    2 / 26 (7.69%)
         occurrences all number
    3
    6
    7
    4
    4
    Pruritus
         subjects affected / exposed
    3 / 26 (11.54%)
    3 / 26 (11.54%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    4 / 26 (15.38%)
         occurrences all number
    4
    3
    0
    0
    4
    Dry skin
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    2 / 26 (7.69%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    2
    0
    0
    Itchy skin
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    2 / 26 (7.69%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    0
    0
    5
    0
    0
    Renal and urinary disorders
    Proteinuria
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    2 / 26 (7.69%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    0
    0
    3
    0
    0
    Raised creatinine
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    2 / 26 (7.69%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    0
    1
    2
    0
    0
    Musculoskeletal and connective tissue disorders
    Non cardiac chest pain
         subjects affected / exposed
    4 / 26 (15.38%)
    3 / 26 (11.54%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    3 / 26 (11.54%)
         occurrences all number
    4
    4
    1
    0
    3
    Leg pain
         subjects affected / exposed
    2 / 26 (7.69%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    2
    0
    1
    0
    0
    Back pain
         subjects affected / exposed
    1 / 26 (3.85%)
    2 / 26 (7.69%)
    4 / 26 (15.38%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    1
    2
    4
    0
    1
    Joint pain
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    3 / 26 (11.54%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    0
    0
    4
    0
    0
    Parasthesia
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    2 / 26 (7.69%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    0
    0
    3
    0
    0
    Osteoarthritis
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    2 / 26 (7.69%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    0
    0
    4
    0
    0
    Infections and infestations
    Upper respiratory tract infection
         subjects affected / exposed
    6 / 26 (23.08%)
    1 / 26 (3.85%)
    1 / 26 (3.85%)
    1 / 26 (3.85%)
    3 / 26 (11.54%)
         occurrences all number
    8
    1
    1
    1
    3
    Urinary tract infection
         subjects affected / exposed
    1 / 26 (3.85%)
    3 / 26 (11.54%)
    1 / 26 (3.85%)
    1 / 26 (3.85%)
    3 / 26 (11.54%)
         occurrences all number
    1
    3
    1
    1
    4
    COVID-19
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    2 / 26 (7.69%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    Chest infection
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    0
    0
    0
    2
    Infection
         subjects affected / exposed
    2 / 26 (7.69%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    2
    0
    1
    0
    2
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    10 / 26 (38.46%)
    8 / 26 (30.77%)
    3 / 26 (11.54%)
    2 / 26 (7.69%)
    2 / 26 (7.69%)
         occurrences all number
    11
    9
    3
    2
    2
    Hypophosphataemia
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    2 / 26 (7.69%)
    1 / 26 (3.85%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    3
    1
    2
    Weight loss
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    3 / 26 (11.54%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    0
    0
    4
    0
    0
    Anorexia
         subjects affected / exposed
    0 / 26 (0.00%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    0
    1
    0
    2

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    03 Aug 2018
    MiST-1, SA01: Updated to version 3.0 following an amendment to the statistical design of the study.
    12 Dec 2018
    MiST-1, SA02: Change CI & Protocol V4
    25 Mar 2019
    MiST-2, SA03: Addition of MiST 2
    01 May 2019
    MiST-2, SA05: Resubmission of MiST 2 addition after GNA
    07 May 2019
    MiST-1, SA04: Master & MiST 1 protocols v5.0 & uploaded IB
    14 Jun 2019
    MiST-4, SA06: Addition of MiST 4
    24 Jul 2019
    MiST-3, SA07: Addition of MiST 3
    01 Sep 2019
    MiST-1, SA08: MiST 1 Protocol V6.0
    01 Dec 2019
    MiST-1, SA09: Changes to stats section, Protocol v7.0
    01 Jan 2020
    MiST-2, SA10: Changes to stats section, Protocol v3.0
    01 Feb 2020
    MiST-4, SA11: Changes to stats section, Protocol v2.0
    01 May 2020
    MiST-2, SA12: COVID-19 adjustments, Patient safety letter Protocol v4.0
    01 Jul 2020
    MiST-4, SA13: Removal of PD-L1 requirement Protocol v3.0
    09 Sep 2020
    Master MiST, SA14: Add text re: MiST 5 and update re: MiST 4 being an all comers arm Protocol v6.0
    23 Sep 2020
    MiST-2, SA15: Patient safety letter (Protocol v4.0 unchanged)
    09 Nov 2020
    MiST-3, SA16: Update to MSD QP details in preparation for Brexit
    30 Nov 2020
    MiST-5, SA17: Addition of the MiST 5 arm
    07 Dec 2020
    MiST-3, SA18: Updated lbs, stats analysis change, update to PIS
    28 Jan 2021
    MiST-5, SA19: Addition of the MiST 5 arm (re-submission following MHRA GNA of SA17)
    12 Mar 2021
    Mist-5, SA20: COVID Adaptations and change to MHRA products form
    12 Mar 2021
    MiST-3, SA22: MHRA Products Form updated with new MIA number
    18 Mar 2021
    MiST-4, SA21: Update IB and PIS
    01 Jun 2021
    MiST-3, SA23: Update RSI, Protocol changes and updated PIS
    08 Feb 2022
    MiST-5, SA24: Updated Niraparib IB and RSI, updated protocol and PIS, new patient diary and end date extension
    11 May 2022
    MiST-3, SA25: Update RSI for both IMPs
    06 Jul 2022
    MiST-5, SA26: Updated CTA with new MA number and QP release addresses
    16 Nov 2022
    MiST-5, SA27: IB update for Dostarlimab and Niraparib, updated PIS side effects and pregnancy
    16 Feb 2023
    Master & MiST-3 & MiST-5, SA28: Mater MiST, M3 and M5
    22 Jul 2024
    MiST-5, SA29: IB update for Dostarlimab and Niraparib, updated PIS side effects and pregnancy

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    19 Mar 2020
    In light of the situation with COVID-19 research capacity was reduce significantly in the coming weeks, therefore this action was taken to prioritise treatment and maximise patient safety for those patients already on the study.
    -

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