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    Clinical Trial Results:
    A Phase 2/3 Study to Evaluate the Efficacy and Safety of Unesbulin in Unresectable or Metastatic, Relapsed or Refractory Leiomyosarcoma

    Summary
    EudraCT number
    		 2022-000073-12
    Trial protocol
    		 HU   ES   DE   IT   PL   NL   FR  
    Global end of trial date
    17 Jul 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    20 Jun 2025
    First version publication date
    20 Jun 2025
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    PTC596-ONC-008-LMS
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT05269355
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    PTC Therapeutics, Inc.
    Sponsor organisation address
    500 Warren Corp Centre Dr, Warren, United States, NJ 07059
    Public contact
    Medical Information, PTC Therapeutics, Inc., +011 44 1-866-562-4620, medinfo@ptcbio.com
    Scientific contact
    Medical Information, PTC Therapeutics International Limited, +353 19068700, medinfo@ptcbio.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
    17 Jul 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    17 Jul 2024
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective was to assess progression-free survival (PFS) of unesbulin plus dacarbazine versus placebo plus dacarbazine.
    Protection of trial subjects
    This study was conducted in accordance with the ethical principles of Good Clinical Practice, according to the International Council for Harmonisation (ICH) Harmonized Tripartite Guideline.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    23 May 2022
    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 States: 202
    Country: Number of subjects enrolled
    Australia: 9
    Country: Number of subjects enrolled
    Brazil: 26
    Country: Number of subjects enrolled
    Canada: 33
    Country: Number of subjects enrolled
    France: 26
    Country: Number of subjects enrolled
    Hungary: 11
    Country: Number of subjects enrolled
    Italy: 2
    Country: Number of subjects enrolled
    Netherlands: 1
    Country: Number of subjects enrolled
    Poland: 1
    Country: Number of subjects enrolled
    Spain: 18
    Country: Number of subjects enrolled
    United Kingdom: 27
    Country: Number of subjects enrolled
    Germany: 2
    Worldwide total number of subjects
    358
    EEA total number of subjects
    61
    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)
    256
    From 65 to 84 years
    101
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Participants were randomized 2:1 to 1 of the following treatment groups: 1. Unesbulin and Dacarbazine (N=239) or 2. Placebo and Dacarbazine (N=120). A total of 359 participants were randomized, of which 358 participants were treated.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Unesbulin and Dacarbazine
    Arm description
    		 Participants received unesbulin 300 milligrams (mg) tablets administered orally twice weekly in each 3-week treatment cycle in combination with dacarbazine 1000 mg/square meter (m^2) intravenously (IV) once every 21 days. Treatment was continued for each participant until evidence of unacceptable toxicity, disease progression, or treatment discontinuation for another reason.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Unesbulin
    Investigational medicinal product code
    PTC596
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Unesbulin was administered per schedule specified in the arm description.

    Investigational medicinal product name
    Dacarbazine
    Investigational medicinal product code
    DTIC
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dacarbazine was administered per schedule specified in the arm description.

    Arm title
    		 Placebo and Dacarbazine
    Arm description
    		 Participants received placebo matching to unesbulin tablets administered orally twice weekly in each 3-week treatment cycle in combination with dacarbazine 1000 mg/m^2 IV once every 21 days. Treatment was continued for each participant until evidence of unacceptable toxicity, disease progression, or treatment discontinuation for another reason.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    PTC596
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo matched to unesbulin was administered per schedule specified in the arm description.

    Investigational medicinal product name
    Dacarbazine
    Investigational medicinal product code
    DTIC
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dacarbazine was administered per schedule specified in the arm description.

    Number of subjects in period 1
    		Unesbulin and Dacarbazine Placebo and Dacarbazine
    Started
    238
    120
    Received at Least 1 Dose of Study Drug
    238
    120
    Completed
    0
    0
    Not completed
    238
    120
         Adverse event, serious fatal
    3
    5
         Consent withdrawn by subject
    18
    5
         Physician decision
    6
    4
         Other Than Specified
    5
    1
         Adverse event, non-fatal
    15
    8
         Progressive Disease
    104
    68
         Study Terminated by Sponsor
    87
    29

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Unesbulin and Dacarbazine
    Reporting group description
    		 Participants received unesbulin 300 milligrams (mg) tablets administered orally twice weekly in each 3-week treatment cycle in combination with dacarbazine 1000 mg/square meter (m^2) intravenously (IV) once every 21 days. Treatment was continued for each participant until evidence of unacceptable toxicity, disease progression, or treatment discontinuation for another reason.

    Reporting group title
    Placebo and Dacarbazine
    Reporting group description
    		 Participants received placebo matching to unesbulin tablets administered orally twice weekly in each 3-week treatment cycle in combination with dacarbazine 1000 mg/m^2 IV once every 21 days. Treatment was continued for each participant until evidence of unacceptable toxicity, disease progression, or treatment discontinuation for another reason.

    Reporting group values
    		 Unesbulin and Dacarbazine Placebo and Dacarbazine Total
    Number of subjects
    		 238 120 358
    Age categorical
    Units: Subjects
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 57.4 ( 10.98 ) 58.6 ( 11.04 ) -
    Sex: Female, Male
    Units: participants
        Female
    		 187 93 280
        Male
    		 51 27 78
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 36 26 62
        Not Hispanic or Latino
    		 170 87 257
        Unknown or Not Reported
    		 32 7 39
    Race
    Units: Subjects
        Asian
    		 17 8 25
        American Indian/Alaska Native
    		 0 1 1
        Black/African American
    		 20 6 26
        Native Hawaiian/Other Pacific Islander
    		 1 0 1
        White/Caucasian
    		 157 92 249
        Other
    		 38 12 50
        Missing
    		 2 1 3
        Multiple
    		 3 0 3

    End points

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    End points reporting groups
    Reporting group title
    Unesbulin and Dacarbazine
    Reporting group description
    		 Participants received unesbulin 300 milligrams (mg) tablets administered orally twice weekly in each 3-week treatment cycle in combination with dacarbazine 1000 mg/square meter (m^2) intravenously (IV) once every 21 days. Treatment was continued for each participant until evidence of unacceptable toxicity, disease progression, or treatment discontinuation for another reason.

    Reporting group title
    Placebo and Dacarbazine
    Reporting group description
    		 Participants received placebo matching to unesbulin tablets administered orally twice weekly in each 3-week treatment cycle in combination with dacarbazine 1000 mg/m^2 IV once every 21 days. Treatment was continued for each participant until evidence of unacceptable toxicity, disease progression, or treatment discontinuation for another reason.

    Primary: Progression Free Survival (PFS) Per Independent Central Review Using Response Evaluation Criteria in Solid Tumors (RECIST) V1.1

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    End point title
    		 Progression Free Survival (PFS) Per Independent Central Review Using Response Evaluation Criteria in Solid Tumors (RECIST) V1.1
    End point description
    PFS was defined as the time from randomization to the documented disease progression or death due to any cause, whichever occurred first. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). The appearance of one or more new lesions was also considered progression. The modified intent-to-treat (mITT) set included randomized participants with 1 to 3 prior lines of therapy.
    End point type
    Primary
    End point timeframe
    Up to approximately 2 years
    End point values
    		 Unesbulin and Dacarbazine Placebo and Dacarbazine
    Number of subjects analysed
    209
    105
    Units: months
        median (confidence interval 95%)
    3.6 (2.8 to 5.5)
    2.6 (1.5 to 3.0)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Unesbulin and Dacarbazine v Placebo and Dacarbazine
    Number of subjects included in analysis
    314
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0017
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.61
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.45
         upper limit
    		 0.83

    Secondary: Objective Response Rate (ORR) Per Independent Central Review Using RECIST V1.1

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    End point title
    		 Objective Response Rate (ORR) Per Independent Central Review Using RECIST V1.1
    End point description
    ORR was defined as percentage of participants who achieved a confirmed best overall response (BOR) of complete response (CR) or partial response (PR). CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The mITT set included randomized participants with 1 to 3 prior lines of therapy.
    End point type
    Secondary
    End point timeframe
    Up to approximately 2 years
    End point values
    		 Unesbulin and Dacarbazine Placebo and Dacarbazine
    Number of subjects analysed
    209
    105
    Units: percentage of participants
        number (confidence interval 95%)
    8.1 (4.7 to 12.8)
    2.1 (0.3 to 7.3)
    No statistical analyses for this end point

    Secondary: Disease Control Rate (DCR) Per Independent Central Review Using RECIST V1.1

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    End point title
    		 Disease Control Rate (DCR) Per Independent Central Review Using RECIST V1.1
    End point description
    DCR was defined as percentage of participants who achieved a confirmed BOR of CR, PR, or at least 3 months of stable disease (SD). CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. The mITT set included randomized participants with 1 to 3 prior lines of therapy.
    End point type
    Secondary
    End point timeframe
    Up to approximately 2 years
    End point values
    		 Unesbulin and Dacarbazine Placebo and Dacarbazine
    Number of subjects analysed
    209
    105
    Units: percentage of participants
        number (confidence interval 95%)
    36.4 (29.7 to 43.5)
    27.1 (18.5 to 37.1)
    No statistical analyses for this end point

    Secondary: Overall Survival

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    End point title
    		 Overall Survival
    End point description
    Overall survival was defined as the time in months from the randomization date to the date of death from any cause or date last known alive for those who did not die. The mITT set included randomized participants with 1 to 3 prior lines of therapy. '9999' represents 'due to limited number of participants with an event, median and upper limit of 95% confidence interval (CI) could not be calculated.'
    End point type
    Secondary
    End point timeframe
    Up to approximately 2 years
    End point values
    		 Unesbulin and Dacarbazine Placebo and Dacarbazine
    Number of subjects analysed
    209
    105
    Units: months
        median (confidence interval 95%)
    9999 (10.4 to 9999)
    9999 (11.0 to 9999)
    No statistical analyses for this end point

    Secondary: Duration of Response Per Independent Central Review Using RECIST V1.1

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    End point title
    		 Duration of Response Per Independent Central Review Using RECIST V1.1
    End point description
    Duration of response was defined as the time from the date of first confirmed response of CR or PR to the date of the first documented disease progression or death due to any cause, whichever occurred first. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Disease progression: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. The mITT set included randomized participants with 1 to 3 prior lines of therapy. '0.999 and 9999' represents 'due to limited number of participants with an event, data could not be calculated.'
    End point type
    Secondary
    End point timeframe
    Up to approximately 2 years
    End point values
    		 Unesbulin and Dacarbazine Placebo and Dacarbazine
    Number of subjects analysed
    209
    105
    Units: months
        median (confidence interval 95%)
    6.87 (0.999 to 9999)
    9999 (9999 to 9999)
    No statistical analyses for this end point

    Secondary: Number of Participants with Treatment-emergent Adverse Events (TEAEs)

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    End point title
    		 Number of Participants with Treatment-emergent Adverse Events (TEAEs)
    End point description
    An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. A TEAE was defined as an AE that had an onset date on or after the first dose of study drug until 30 days after last dose or occurred prior to first dose of study drug and worsened in severity after first dose of study drug. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'. The safety analysis set included all participants who received at least 1 dose of study drug (unesbulin/placebo or dacarbazine).
    End point type
    Secondary
    End point timeframe
    From first dose of study drug up to approximately 2 years
    End point values
    		 Unesbulin and Dacarbazine Placebo and Dacarbazine
    Number of subjects analysed
    238
    120
    Units: participants
    236
    112
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first dose of study drug up to approximately 2 years
    Adverse event reporting additional description
    The safety analysis set included all participants who received at least 1 dose of study drug (unesbulin/placebo or dacarbazine).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.0
    Reporting groups
    Reporting group title
    Placebo and Dacarbazine
    Reporting group description
    		 Participants received placebo matching to unesbulin tablets administered orally twice weekly in each 3-week treatment cycle in combination with dacarbazine 1000 mg/m^2 IV once every 21 days. Treatment was continued for each participant until evidence of unacceptable toxicity, disease progression, or treatment discontinuation for another reason.

    Reporting group title
    Unesbulin and Dacarbazine
    Reporting group description
    		 Participants received unesbulin 300 mg tablets administered orally twice weekly in each 3-week treatment cycle in combination with dacarbazine 1000 mg/m^2 IV once every 21 days. Treatment was continued for each participant until evidence of unacceptable toxicity, disease progression, or treatment discontinuation for another reason.

    Serious adverse events
    		 Placebo and Dacarbazine Unesbulin and Dacarbazine
    Total subjects affected by serious adverse events
         subjects affected / exposed
    43 / 120 (35.83%)
    81 / 238 (34.03%)
         number of deaths (all causes)
    27
    49
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour pain
         subjects affected / exposed
    0 / 120 (0.00%)
    3 / 238 (1.26%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant neoplasm progression
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to lung
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tumour haemorrhage
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Hypotension
         subjects affected / exposed
    2 / 120 (1.67%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    1 / 120 (0.83%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Disease progression
         subjects affected / exposed
    5 / 120 (4.17%)
    3 / 238 (1.26%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 5
    0 / 3
    Fatigue
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 120 (0.83%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    5 / 120 (4.17%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    2 / 5
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Systemic inflammatory response syndrome
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Vaginal haemorrhage
    Additional description: This is a sex-specific AE. Only female participants were at risk.
         subjects affected / exposed [1]
    0 / 93 (0.00%)
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion
         subjects affected / exposed
    6 / 120 (5.00%)
    2 / 238 (0.84%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Respiratory failure
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pulmonary embolism
         subjects affected / exposed
    0 / 120 (0.00%)
    2 / 238 (0.84%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pneumothorax
         subjects affected / exposed
    1 / 120 (0.83%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleuritic pain
         subjects affected / exposed
    1 / 120 (0.83%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Suicidal ideation
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Product issues
    Device occlusion
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Blood bilirubin increased
         subjects affected / exposed
    1 / 120 (0.83%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Electrocardiogram QT prolonged
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutrophil count decreased
         subjects affected / exposed
    1 / 120 (0.83%)
    2 / 238 (0.84%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    1 / 120 (0.83%)
    5 / 238 (2.10%)
         occurrences causally related to treatment / all
    1 / 1
    5 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transaminases increased
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    White blood cell count decreased
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Accidental overdose
         subjects affected / exposed
    0 / 120 (0.00%)
    2 / 238 (0.84%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infusion related reaction
         subjects affected / exposed
    1 / 120 (0.83%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Overdose
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Toxicity to various agents
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Aplasia
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial flutter
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial thrombosis
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial tachycardia
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 120 (0.83%)
    2 / 238 (0.84%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiac failure
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bundle branch block left
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Central nervous system lesion
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain oedema
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Facial paralysis
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neurotoxicity
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal cord compression
         subjects affected / exposed
    1 / 120 (0.83%)
    2 / 238 (0.84%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    3 / 120 (2.50%)
    5 / 238 (2.10%)
         occurrences causally related to treatment / all
    2 / 3
    4 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    2 / 120 (1.67%)
    6 / 238 (2.52%)
         occurrences causally related to treatment / all
    2 / 2
    7 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    2 / 120 (1.67%)
    4 / 238 (1.68%)
         occurrences causally related to treatment / all
    1 / 2
    5 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematotoxicity
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    0 / 120 (0.00%)
    8 / 238 (3.36%)
         occurrences causally related to treatment / all
    0 / 0
    9 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bicytopenia
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    1 / 120 (0.83%)
    3 / 238 (1.26%)
         occurrences causally related to treatment / all
    0 / 1
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Colitis
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain lower
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    2 / 120 (1.67%)
    3 / 238 (1.26%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 120 (0.00%)
    2 / 238 (0.84%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 120 (0.83%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestine perforation
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal perforation
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Haemoperitoneum
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 120 (0.83%)
    2 / 238 (0.84%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 120 (0.00%)
    2 / 238 (0.84%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 120 (0.83%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Subcapsular hepatic haematoma
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic failure
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Renal and urinary disorders
    Urinary tract obstruction
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute kidney injury
         subjects affected / exposed
    1 / 120 (0.83%)
    2 / 238 (0.84%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 120 (0.83%)
    2 / 238 (0.84%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal pain
         subjects affected / exposed
    1 / 120 (0.83%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Device related sepsis
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    1 / 120 (0.83%)
    5 / 238 (2.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Bronchitis
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pertussis
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 120 (0.83%)
    3 / 238 (1.26%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    3 / 120 (2.50%)
    4 / 238 (1.68%)
         occurrences causally related to treatment / all
    2 / 3
    3 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Soft tissue infection
         subjects affected / exposed
    1 / 120 (0.83%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal cord infection
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 120 (0.83%)
    2 / 238 (0.84%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular device infection
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 238 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    1 / 120 (0.83%)
    2 / 238 (0.84%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malnutrition
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 238 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Notes
    [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: This is a sex-specific AE. Only female participants were at risk.
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo and Dacarbazine Unesbulin and Dacarbazine
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    112 / 120 (93.33%)
    234 / 238 (98.32%)
    Investigations
    White blood cell count decreased
         subjects affected / exposed
    9 / 120 (7.50%)
    36 / 238 (15.13%)
         occurrences all number
    20
    83
    Platelet count decreased
         subjects affected / exposed
    17 / 120 (14.17%)
    51 / 238 (21.43%)
         occurrences all number
    42
    114
    Neutrophil count decreased
         subjects affected / exposed
    13 / 120 (10.83%)
    60 / 238 (25.21%)
         occurrences all number
    28
    140
    Blood creatinine increased
         subjects affected / exposed
    5 / 120 (4.17%)
    13 / 238 (5.46%)
         occurrences all number
    6
    28
    Aspartate aminotransferase increased
         subjects affected / exposed
    8 / 120 (6.67%)
    20 / 238 (8.40%)
         occurrences all number
    10
    27
    Alanine aminotransferase increased
         subjects affected / exposed
    10 / 120 (8.33%)
    18 / 238 (7.56%)
         occurrences all number
    13
    27
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    10 / 120 (8.33%)
    32 / 238 (13.45%)
         occurrences all number
    13
    35
    Dysgeusia
         subjects affected / exposed
    2 / 120 (1.67%)
    17 / 238 (7.14%)
         occurrences all number
    2
    19
    Headache
         subjects affected / exposed
    14 / 120 (11.67%)
    29 / 238 (12.18%)
         occurrences all number
    16
    42
    Neuropathy peripheral
         subjects affected / exposed
    4 / 120 (3.33%)
    15 / 238 (6.30%)
         occurrences all number
    4
    21
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    35 / 120 (29.17%)
    103 / 238 (43.28%)
         occurrences all number
    91
    260
    Thrombocytopenia
         subjects affected / exposed
    27 / 120 (22.50%)
    75 / 238 (31.51%)
         occurrences all number
    76
    238
    Neutropenia
         subjects affected / exposed
    23 / 120 (19.17%)
    88 / 238 (36.97%)
         occurrences all number
    53
    298
    Leukopenia
         subjects affected / exposed
    7 / 120 (5.83%)
    15 / 238 (6.30%)
         occurrences all number
    17
    81
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    12 / 120 (10.00%)
    27 / 238 (11.34%)
         occurrences all number
    24
    69
    Fatigue
         subjects affected / exposed
    44 / 120 (36.67%)
    93 / 238 (39.08%)
         occurrences all number
    51
    135
    Pyrexia
         subjects affected / exposed
    9 / 120 (7.50%)
    15 / 238 (6.30%)
         occurrences all number
    10
    17
    Oedema peripheral
         subjects affected / exposed
    12 / 120 (10.00%)
    20 / 238 (8.40%)
         occurrences all number
    13
    22
    Non-cardiac chest pain
         subjects affected / exposed
    5 / 120 (4.17%)
    15 / 238 (6.30%)
         occurrences all number
    6
    19
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    44 / 120 (36.67%)
    115 / 238 (48.32%)
         occurrences all number
    62
    153
    Diarrhoea
         subjects affected / exposed
    27 / 120 (22.50%)
    131 / 238 (55.04%)
         occurrences all number
    36
    216
    Constipation
         subjects affected / exposed
    19 / 120 (15.83%)
    50 / 238 (21.01%)
         occurrences all number
    23
    57
    Abdominal pain upper
         subjects affected / exposed
    6 / 120 (5.00%)
    13 / 238 (5.46%)
         occurrences all number
    6
    13
    Vomiting
         subjects affected / exposed
    17 / 120 (14.17%)
    43 / 238 (18.07%)
         occurrences all number
    20
    61
    Abdominal pain
         subjects affected / exposed
    11 / 120 (9.17%)
    42 / 238 (17.65%)
         occurrences all number
    13
    50
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    10 / 120 (8.33%)
    29 / 238 (12.18%)
         occurrences all number
    12
    33
    Dyspnoea
         subjects affected / exposed
    23 / 120 (19.17%)
    26 / 238 (10.92%)
         occurrences all number
    25
    32
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    4 / 120 (3.33%)
    14 / 238 (5.88%)
         occurrences all number
    4
    14
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    12 / 120 (10.00%)
    20 / 238 (8.40%)
         occurrences all number
    15
    23
    Back pain
         subjects affected / exposed
    13 / 120 (10.83%)
    22 / 238 (9.24%)
         occurrences all number
    15
    24
    Myalgia
         subjects affected / exposed
    5 / 120 (4.17%)
    19 / 238 (7.98%)
         occurrences all number
    5
    26
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    8 / 120 (6.67%)
    14 / 238 (5.88%)
         occurrences all number
    8
    22
    COVID-19
         subjects affected / exposed
    9 / 120 (7.50%)
    13 / 238 (5.46%)
         occurrences all number
    9
    15
    Metabolism and nutrition disorders
    Hyperglycaemia
         subjects affected / exposed
    7 / 120 (5.83%)
    11 / 238 (4.62%)
         occurrences all number
    10
    12
    Decreased appetite
         subjects affected / exposed
    14 / 120 (11.67%)
    37 / 238 (15.55%)
         occurrences all number
    16
    46

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    31 Jan 2022
    The overall reason for this version of the protocol was to modify the timing and description of the interim analysis for futility and efficacy evaluation. - The lower limit of Grade 1 thrombocytopenia platelet count was changed from 750000 to 75000. - The timing and description of the interim analysis for futility and efficacy evaluation were modified.
    28 Apr 2023
    The overall reason for this version of the protocol was to incorporate comprehensively all modifications requested by country-specific health authorities and Ethics Committees in response to the Clinical Trial Application. Additional updates were made for improved clarity and study conduct. - It was specified that Overall Survival was the key secondary endpoint. Additional details describing the analysis of this key secondary endpoint were added to the Synopsis. - It was clarified that no dose reduction of unesbulin/placebo was permitted. - An exception to Inclusion Criterion was added for participants with Gilbert’s syndrome who had elevated bilirubin values. - Inclusion Criterion was modified to increase the eligibility limit for aspartate aminotransferase and alanine aminotransferase from 1.5 to 3 times the upper limit of normal. - It was clarified in Inclusion Criterion that prior lines of treatment may include but were not limited to single-agent doxorubicin or other anthracycline, doxorubicin plus ifosfamide, trabectedin, pazopanib, or gemcitabine with or without docetaxel. - Administration of live vaccines was added as an Exclusion Criterion and as a concomitant medication. - It was clarified that survival follow-up would continue every 3 months as per the Schedule of Assessments. - Treatment-emergent adverse events were defined.
    28 Nov 2023
    The main reasons for this version were to clarify study procedures in cases of DTIC interruption and revise the analysis of the key secondary endpoint (Overall Survival). Additional updates were made to reflect changes in study staff, improved clarity, and to address clerical errors. - It was clarified that a hierarchical testing procedure would be utilized. - For participants who have DTIC interrupted or held, it was added that clinical laboratory assessments would be required weekly for the first 3 weeks after DTIC reintroduction. For subsequent cycles, the clinical laboratory assessments could be performed at a minimum of once per cycle or more frequently per the investigator’s discretion to ensure that the participant met the protocol-defined safety criteria. - The following statement was added: "DTIC should be reintroduced at least 48 hours after unesbulin 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.
    The study was terminated early due to business decision.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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