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    Clinical Trial Results:
    The ROME trial from histology to target: the road to personalize target therapy and immunotherapy

    Summary
    EudraCT number
    		 2018-002190-21
    Trial protocol
    		 IT  
    Global end of trial date
    06 Sep 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    14 Sep 2025
    First version publication date
    14 Sep 2025
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    MAR-BAS-18-005
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04591431
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Fondazione per la Medicina Personalizzata
    Sponsor organisation address
    Viale Regina Margherita, 302, ROMA, Italy, 00198
    Public contact
    Clinical Trial Unit, Fondazione per la Medicina Personalizzata, 39 3208630311, silvia.violetti@clinicaltrialsfmp.it
    Scientific contact
    Clinical Trial Unit, Fondazione per la Medicina Personalizzata, 39 06 83977939, silvia.violetti@clinicaltrialsfmp.it
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    30 Jan 2025
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    06 Sep 2024
    Global end of trial reached?
    Yes
    Global end of trial date
    06 Sep 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of our study is to evaluate the efficacy analyses (meant as overall response rate ORR) of TT vs SoC. The main efficacy analyses were conducted on the modified ITT population composed by 400 patients. The safety data regard the SAFETY population which consisted in the patients exposed to the study treatments, i.e. the randomized patients who assumed one dose of treatment at least. The SAFETY population was composed by 362 patients
    Protection of trial subjects
    On 29/11/2022, the Data Monitoring Board met in accordance with the clinical protocol, having reached 20% enrolment of randomised patients. The database data was locked on 31 October 2022 and patients data were extracted. After reviewing the data, DSUR and other documentation, the Board did not identify any safety issues related to the treatments assigned to patients or any futility of the study. It therefore recommended the continuation of the study.
    Background therapy
    		 Since these were cancer patients with various conditions treated in different hospitals, the concomitant drugs assigned were those used in clinical practice at the various hospitals.
    Evidence for comparator
    		 Recent studies have shown that targeted agents are superior to standard non-targeted treatments. Therefore, the ROME study could contribute to the evaluation of the impact of personalised therapies in different types of tumours based on the patient's genomic profile vs Standard of Care treatments. This approach could be extended to all other cancer histologies in which the second or third line of treatment has not well defined, has unsatisfactory clinical outcomes or is lack of well-defined therapeutic targets.
    Actual start date of recruitment
    13 Oct 2020
    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
    Italy: 400
    Worldwide total number of subjects
    400
    EEA total number of subjects
    400
    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)
    250
    From 65 to 84 years
    149
    85 years and over
    1

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Eligible participants were adult patients with advanced solid tumors, ECOG performance status 0–1, and measurable disease per RECIST/iRECIST. Molecular profiling was required prior to randomization based on inclusion and exclusion criteria.

    Pre-assignment
    Screening details
    		 Patients with progressive disease of breast cancer, metastatic gastro-intestinal tumors, non small cell lung cancer (NSCLC) or others. Patients should have completed or failed at least 1 line of treatment and no more than 2. Patients who are candidates to potentially curative surgery or other locoregional treatment are excluded

    Pre-assignment period milestones
    Number of subjects started
    		 400
    Number of subjects completed
    		 400

    Period 1
    Period 1 title
    TREATMENT PHASE (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded
    Blinding implementation details
    Not applicable

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 ARM A: SoC
    Arm description
    		 Patients will be treated with standard therapy according the current version of the AIOM guidelines for their type of cancer. At the first PD the patient switched to the Tailored Treatment defined by Molecular Tumor Board at the time of randomization. The patient stayed in the study until the occurrence of a second PD or 18 months after randomization.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Oncological Standard of Care Treatment
    Investigational medicinal product code
    Other name
    All the oncological treatments according to the current version of the AIOM guidelines
    Pharmaceutical forms
    Coated tablet, Concentrate and solvent for intravesical solution, Concentrate and solvent for solution for infusion, Concentrate and solvent for solution for injection/infusion, Injection/infusion, Capsule
    Routes of administration
    Cutaneous use, Infusion , Instillation , Oral use, Other use
    Dosage and administration details
    Farmaceutical forms and route of administration were performed according to the relevant clinical practice

    Arm title
    		 ARM B: TT
    Arm description
    		 TAILORED THERAPY according to the genomic profile. Patients were treated with target therapy and/or immunotherapy according to their genomic profile evidenced by the liquid and tissue profiling. Patients were treated with one or more drugs of the following list, if a safe combination is avalaible in a phase II trial already conducted. At the first PD, patient switched to SoC until the occurrence of a second PD or 18 months after randomization
    Arm type
    		 Experimental

    Investigational medicinal product name
    Erlotinib
    Investigational medicinal product code
    Other name
    Tarceva
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    150/100 mg/die according to the tumor type

    Investigational medicinal product name
    TRASTUZUMAB
    Investigational medicinal product code
    Other name
    Herceptin
    Pharmaceutical forms
    Solution for infusion in administration system
    Routes of administration
    Infusion
    Dosage and administration details
    8-4mg/kg/week according to the tumor type. the maintenance dose reduced to 6-2mg/kg/week respectively

    Investigational medicinal product name
    Pertuzumab
    Investigational medicinal product code
    Other name
    Perjeta
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Infusion
    Dosage and administration details
    8 mg/kg/week followed by 6 mg/kg /3 weeks for maintenance

    Investigational medicinal product name
    Trastuzumab Emtansine
    Investigational medicinal product code
    Other name
    Kadcyla
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Infusion
    Dosage and administration details
    3,6 mg/kg/3 weeks

    Investigational medicinal product name
    Vemurafenib
    Investigational medicinal product code
    Other name
    Zelboraf
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    960 mg bid

    Investigational medicinal product name
    Cobimetinib
    Investigational medicinal product code
    Other name
    Cotellic
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    60 mg/die

    Investigational medicinal product name
    Alectinib
    Investigational medicinal product code
    Other name
    Alecensa
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    600 mg bid

    Investigational medicinal product name
    Vismogedib
    Investigational medicinal product code
    Other name
    Erivedge
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    150 mg die

    Investigational medicinal product name
    Atezolizumab
    Investigational medicinal product code
    Other name
    Tecentriq
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Infusion
    Dosage and administration details
    • 840 mg every two weeks • 1200 mg every three weeks • 1680 mg every four weeks.

    Investigational medicinal product name
    Ipatasertib
    Investigational medicinal product code
    RO5532961
    Other name
    GDC-0068, G-035608
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    400 mg/die scalable down to 200 mg/die according to safety condition

    Investigational medicinal product name
    Entrectinib
    Investigational medicinal product code
    Other name
    Rozlytrek
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    600 mg die scalable down to 200 mg according to safety condition

    Investigational medicinal product name
    Everolimus
    Investigational medicinal product code
    Other name
    Afinitor
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    10 mg once a day

    Investigational medicinal product name
    Palbociclib
    Investigational medicinal product code
    Other name
    Ibrance
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    125 mg once daily

    Investigational medicinal product name
    Lapatinib
    Investigational medicinal product code
    Other name
    Tyverb
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1250 mg die

    Investigational medicinal product name
    Ipilimumab
    Investigational medicinal product code
    Other name
    Yervoy
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Infusion
    Dosage and administration details
    3 mg/kg every 3 weeks

    Investigational medicinal product name
    Nivolumab
    Investigational medicinal product code
    Other name
    Opdivo
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Infusion
    Dosage and administration details
    240 mg every 2 weeks or 480 mg every 4 weeks

    Investigational medicinal product name
    Brigatinib
    Investigational medicinal product code
    Other name
    Alunbrig
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    90 mg orally once daily for the first 7 days; when tolerated, increased to 180 mg orally once daily.

    Investigational medicinal product name
    Ponatinib
    Investigational medicinal product code
    Other name
    Iclusig
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    45 mg die scalable down to 15 mg die according to safety condition

    Investigational medicinal product name
    Itacitinib
    Investigational medicinal product code
    INCB039110
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    600 mg/die scalable down to 200 mg according to safety condition

    Investigational medicinal product name
    Pemigatinib
    Investigational medicinal product code
    INCB054828
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    13.5 mg orally once daily

    Investigational medicinal product name
    Alpelisib
    Investigational medicinal product code
    Other name
    Pigray
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    300 mg once a day scalable down to 200 mg according to safety condition

    Investigational medicinal product name
    Tepotinib
    Investigational medicinal product code
    Other name
    TEPMETKO
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    500 mg one a day scalable down to 250 mg once a day according to safety condition

    Investigational medicinal product name
    Pralsetinib
    Investigational medicinal product code
    Other name
    Gavreto
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    400 mg/die scalable down to 100 mg/die according to safety condition

    Investigational medicinal product name
    Talazoparib
    Investigational medicinal product code
    Other name
    Talzenna
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    1 mg once daily, scalable down to 0.25 mg/die according to safety condition

    Investigational medicinal product name
    Selpercatinib
    Investigational medicinal product code
    Other name
    Retevmo
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    • Less than 50 kg: 120 mg/bid scalable down to 40 mg/bid according to safety condition • 50 kg or greater: 160 mg/bid scalable down to 40 mg/bid according to safety condition

    Number of subjects in period 1
    		ARM A: SoC ARM B: TT
    Started
    200
    200
    Completed
    33
    41
    Not completed
    167
    159
         Adverse event, serious fatal
    38
    36
         Consent withdrawn by subject
    10
    6
         Adverse event, non-fatal
    20
    28
         Lost to follow-up
    5
    2
         Physical deterioration, other deaths
    64
    65
         Protocol deviation
    30
    22

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    ARM A: SoC
    Reporting group description
    		 Patients will be treated with standard therapy according the current version of the AIOM guidelines for their type of cancer. At the first PD the patient switched to the Tailored Treatment defined by Molecular Tumor Board at the time of randomization. The patient stayed in the study until the occurrence of a second PD or 18 months after randomization.

    Reporting group title
    ARM B: TT
    Reporting group description
    		 TAILORED THERAPY according to the genomic profile. Patients were treated with target therapy and/or immunotherapy according to their genomic profile evidenced by the liquid and tissue profiling. Patients were treated with one or more drugs of the following list, if a safe combination is avalaible in a phase II trial already conducted. At the first PD, patient switched to SoC until the occurrence of a second PD or 18 months after randomization

    Reporting group values
    		 ARM A: SoC ARM B: TT Total
    Number of subjects
    		 200 200 400
    Age categorical
    age 18-64; age 65-84; >84
    Units: Subjects
        Adults (18-64 years)
    		 132 118 250
        From 65-84 years
    		 68 81 149
        85 years and over
    		 0 1 1
    Age continuous
    Age at the time of the signed of the Informed Consent
    Units: years
        arithmetic mean (standard deviation)
    		 59.3 ( 11.7 ) 60.4 ( 11.7 ) -
    Gender categorical
    Male and Female
    Units: Subjects
        Female
    		 100 108 208
        Male
    		 100 92 192
    Genetic Profile
    A molecular profile of the cancer was evaluated on tumor tissue biopsy and on ctDNA on 1794 patients. After FO evaluations patients with actionable mutations, not previously identified with other methods, for which approved drugs according to histotype were available, were excluded. Once identified molecular abnormalities (not only those that were disease-specific), that could be modulated with target or immunotherapeutic intervention available within the present study, patients were randomized into Arm A or B to receive therapy
    Units: Subjects
        A Stratum-Breast
    		 20 20 40
        B Stratum_Gastric
    		 55 54 109
        C Stratum_NSCLC
    		 15 16 31
        C Stratum_Other
    		 110 110 220
    Subject analysis sets

    Subject analysis set title
    Baseline characteristics
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    The following baseline characteristics of all the randomized patients were analyzed: Age, Gender, Hospitalization, Race, ECOG PS, Medical and Oncological History, Prior and Concomitant Medication, Hiv, Hbv, Hcv tests

    Subject analysis set title
    Efficacy analysis
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    The following endpoints were analyzed on the mITT population: ORR, OS, PFS, TTTF, TTNT. Moreover, exploratory analyses on MSI-H, hTMB, BRAF mutations, and HER2 alterations groups were analysed with the same analyses, i.e. ORR, OS, PFS, TTTF and TTNT.

    Subject analysis set title
    Safety Analysis
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    The following safety analyses were performed on the safety population exposed to treatment: AEs, Laboratory Data, Vital Signs

    Subject analysis sets values
    		 Baseline characteristics Efficacy analysis Safety Analysis
    Number of subjects
    400
    400
    362
    Age categorical
    age 18-64; age 65-84; >84
    Units: Subjects
        Adults (18-64 years)
    250
    250
    225
        From 65-84 years
    49
    49
    136
        85 years and over
    1
    1
    1
    Age continuous
    Age at the time of the signed of the Informed Consent
    Units: years
        arithmetic mean (standard deviation)
    59.8 ( 11.7 )
    59.8 ( 11.7 )
    59.9 ( 11.8 )
    Gender categorical
    Male and Female
    Units: Subjects
        Female
    208
    208
    188
        Male
    192
    192
    174
    Genetic Profile
    A molecular profile of the cancer was evaluated on tumor tissue biopsy and on ctDNA on 1794 patients. After FO evaluations patients with actionable mutations, not previously identified with other methods, for which approved drugs according to histotype were available, were excluded. Once identified molecular abnormalities (not only those that were disease-specific), that could be modulated with target or immunotherapeutic intervention available within the present study, patients were randomized into Arm A or B to receive therapy
    Units: Subjects
        A Stratum-Breast
    40
    40
    37
        B Stratum_Gastric
    109
    109
    97
        C Stratum_NSCLC
    31
    31
    26
        C Stratum_Other
    220
    220
    202

    End points

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    End points reporting groups
    Reporting group title
    ARM A: SoC
    Reporting group description
    		 Patients will be treated with standard therapy according the current version of the AIOM guidelines for their type of cancer. At the first PD the patient switched to the Tailored Treatment defined by Molecular Tumor Board at the time of randomization. The patient stayed in the study until the occurrence of a second PD or 18 months after randomization.

    Reporting group title
    ARM B: TT
    Reporting group description
    		 TAILORED THERAPY according to the genomic profile. Patients were treated with target therapy and/or immunotherapy according to their genomic profile evidenced by the liquid and tissue profiling. Patients were treated with one or more drugs of the following list, if a safe combination is avalaible in a phase II trial already conducted. At the first PD, patient switched to SoC until the occurrence of a second PD or 18 months after randomization

    Subject analysis set title
    Baseline characteristics
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    The following baseline characteristics of all the randomized patients were analyzed: Age, Gender, Hospitalization, Race, ECOG PS, Medical and Oncological History, Prior and Concomitant Medication, Hiv, Hbv, Hcv tests

    Subject analysis set title
    Efficacy analysis
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    The following endpoints were analyzed on the mITT population: ORR, OS, PFS, TTTF, TTNT. Moreover, exploratory analyses on MSI-H, hTMB, BRAF mutations, and HER2 alterations groups were analysed with the same analyses, i.e. ORR, OS, PFS, TTTF and TTNT.

    Subject analysis set title
    Safety Analysis
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    The following safety analyses were performed on the safety population exposed to treatment: AEs, Laboratory Data, Vital Signs

    Primary: OVERALL RESPONSE RATE by Arm

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    End point title
    		 OVERALL RESPONSE RATE by Arm
    End point description
    Overall Response Rate (ORR) defined as the proportion of patients with a complete response (CR) or partial response (PR)
    End point type
    Primary
    End point timeframe
    OVERALL RESPONSE RATE (ORR) on the entire treatment period
    End point values
    		 ARM A: SoC ARM B: TT
    Number of subjects analysed
    200
    200
    Units: %
        number (not applicable)
    10
    17.5
    Statistical analysis title
    		 Overall Response Rate
    Statistical analysis description
    The results of the primary endpoint are included in the post-text Table 14.2.1a of the CSR. The table includes the analysis on the mITT, ITT and PP populations. All the raw data are included in post-text Listing 16.2.2 of the CSR. The Overall Response Rate (ORR) is defined as the proportion of patients with a complete response (CR) or partial response (PR), across the four predefined tumor strata in the mITT population.
    Comparison groups
    ARM A: SoC v ARM B: TT
    Number of subjects included in analysis
    400
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0285 [1]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [1] - The ORR was significantly higher in the Tailored Therapy group compared to the Standard of Care group, with a Cochran-Mantel-Haenszel p-value of 0.0285, suggesting a potential benefit of molecularly guided treatment strategies.

    Secondary: Progression Free Survival

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    End point title
    		 Progression Free Survival
    End point description
    PFS was evaluated in the modified Intention-to-Treat (mITT) population and is summarized in post-text Table 12.2.3a of the CSR and the corresponding Kaplan-Meier curve. Patients receiving Tailored Therapy (TT) experienced a longer mean PFS of 7.75 months (Standard Error [SE]: 0.61) compared to 4.60 months (SE: 0.36) in the Standard of Care (SoC) arm. Median PFS was also extended in the TT group, at 3.45 months (95% Confidence Interval [CI]: 3.03 to 4.84), versus 2.80 months (95% CI: 2.53 to 3.19) in the SoC group. The hazard ratio (HR) for progression or death was 0.66 (95% CI: 0.53 to 0.82), indicating a statistically significant 34% reduction in the risk of progression or death for patients treated with TT compared to SoC. The 9-month PFS rate was 27.8% (95% CI: 21.4 to 34.2) in the TT arm versus 13.4% (95% CI: 8.4 to 18.5) in the SoC arm, while the 12-month PFS rate was 22.0% (95% CI: 16.0 to 28.0) versus 8.3% (95% CI: 4.2 to 12.5), respectively.
    End point type
    Secondary
    End point timeframe
    PFS during the entire course of the study
    End point values
    		 ARM A: SoC ARM B: TT
    Number of subjects analysed
    200
    200
    Units: month
        median (confidence interval 95%)
    2.8 (2.53 to 3.19)
    3.45 (3.03 to 4.84)
    Statistical analysis title
    		 PROGRESSION FREE SURVIVAL
    Statistical analysis description
    These results demonstrate a clear and clinically meaningful improvement in PFS with Tailored Therapy over Standard of Care, supporting the efficacy of biomarker-guided treatment strategies in this patient population.
    Comparison groups
    ARM B: TT v ARM A: SoC
    Number of subjects included in analysis
    400
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.66
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.53
         upper limit
    		 0.82

    Secondary: OVERALL SURVIVAL

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    End point title
    		 OVERALL SURVIVAL
    End point description
    OS defined as the time from randomization to death from any cause. Data for patients with no record of death were censored at the last date they were known to be alive.
    End point type
    Secondary
    End point timeframe
    OS during the entire course of the study
    End point values
    		 ARM A: SoC ARM B: TT
    Number of subjects analysed
    200
    200
    Units: months
        median (confidence interval 95%)
    7.86 (5.43 to 10.0)
    9.11 (6.78 to 11.02)
    Statistical analysis title
    		 Overall Survival
    Statistical analysis description
    No relevant diffferences were observed between the two arms
    Comparison groups
    ARM A: SoC v ARM B: TT
    Number of subjects included in analysis
    400
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.92
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.72
         upper limit
    		 1.19

    Secondary: Time to Treatment Failure

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    End point title
    		 Time to Treatment Failure
    End point description
    Time to Treatment Failure (TTTF) is defined as the time from randomization or first dose of study treatment until the date of permanent treatment discontinuation for any reason, including disease progression, adverse events, death, or withdrawal from study.
    End point type
    Secondary
    End point timeframe
    TTTF during the entire course of the study
    End point values
    		 ARM A: SoC ARM B: TT
    Number of subjects analysed
    200
    200
    Units: months
        median (confidence interval 95%)
    2.76 (2.53 to 3.06)
    3.49 (3.06 to 4.86)
    Statistical analysis title
    		 TTTF
    Statistical analysis description
    Pts in the Tailored Therapy (TT) arm showed a longer median TTF of 3.49 months (95% Confidence Interval [CI]: 3.06 to 4.87) compared to 2.76 months (95% CI: 2.53 to 3.06) in the Standard of Care (SoC) arm. The hazard ratio (HR) for treatment failure was 0.64 (95% CI: 0.51 to 0.79), demonstrating a 36% reduction in the risk of treatment discontinuation for any reason in the TT arm versus SoC.
    Comparison groups
    ARM A: SoC v ARM B: TT
    Number of subjects included in analysis
    400
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.64
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.51
         upper limit
    		 0.79

    Secondary: Time to Next Treatment

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    End point title
    		 Time to Next Treatment
    End point description
    Time to Next Treatment (TTNT) is defined as the time interval from the date of randomization or first dose of study treatment to the date of initiation of subsequent anticancer therapy after discontinuation of the study treatment, whichever occurs first.
    End point type
    Secondary
    End point timeframe
    TTNT during the entire course of the study
    End point values
    		 ARM A: SoC ARM B: TT
    Number of subjects analysed
    200
    200
    Units: months
        median (confidence interval 95%)
    3.45 (2.99 to 3.75)
    5.03 (3.91 to 6.32)
    Statistical analysis title
    		 Time to Next Treatment
    Statistical analysis description
    The median TTNT was extended in the TT group at 5.03 months (95% Confidence Interval [CI]: 3.91 to 6.32), versus 3.45 months (95% CI: 2.99 to 3.75) in the SoC group. The hazard ratio (HR) for initiation of next treatment was 0.58 (95% CI: 0.46 to 0.73), indicating a statistically significant 42% reduction in the risk of starting subsequent therapy for patients treated with TT compared to SoC.
    Comparison groups
    ARM A: SoC v ARM B: TT
    Number of subjects included in analysis
    400
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.58
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.46
         upper limit
    		 0.73

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All adverse events occurring between the date of informed consent signature and 3 months after last drug administration were collected
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    Arm A: SoC
    Reporting group description
    		 All adverse events were collected by the SoC arm in the safety population.

    Reporting group title
    Arm B: TT
    Reporting group description
    		 All adverse events were collected by the TT arm in the safety population.

    Serious adverse events
    		 Arm A: SoC Arm B: TT
    Total subjects affected by serious adverse events
         subjects affected / exposed
    76 / 179 (42.46%)
    62 / 183 (33.88%)
         number of deaths (all causes)
    110
    113
         number of deaths resulting from adverse events
    42
    39
    Vascular disorders
    Disseminated intravascular coagulation
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Haemorrhage intracranial
         subjects affected / exposed
    1 / 179 (0.56%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Ischaemia
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Surgical and medical procedures
    Hospitalisation
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Disease progression
         subjects affected / exposed
    13 / 179 (7.26%)
    11 / 183 (6.01%)
         occurrences causally related to treatment / all
    1 / 13
    1 / 11
         deaths causally related to treatment / all
    1 / 13
    1 / 10
    General physical health deterioration
         subjects affected / exposed
    12 / 179 (6.70%)
    10 / 183 (5.46%)
         occurrences causally related to treatment / all
    0 / 12
    1 / 10
         deaths causally related to treatment / all
    0 / 12
    1 / 9
    Hyperpyrexia
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    0 / 179 (0.00%)
    2 / 183 (1.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pyrexia
         subjects affected / exposed
    4 / 179 (2.23%)
    3 / 183 (1.64%)
         occurrences causally related to treatment / all
    1 / 4
    1 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Dyspnoea
         subjects affected / exposed
    1 / 179 (0.56%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Interstitial lung disease
         subjects affected / exposed
    2 / 179 (1.12%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    1 / 3
    1 / 1
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 179 (0.56%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    2 / 179 (1.12%)
    2 / 183 (1.09%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    2 / 179 (1.12%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Respiratory failure
         subjects affected / exposed
    1 / 179 (0.56%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Product issues
    Device occlusion
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Blood Bilirubin increased
         subjects affected / exposed
    4 / 179 (2.23%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Blood creatinine increased
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lipase increased
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SARS-CoV-2 test positive
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Transaminases increased
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Osteoradionecrosis
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vaginal cuff dehiscence
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Myocarditis
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 183 (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
    Brain oedema
         subjects affected / exposed
    2 / 179 (1.12%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cognitive disorder
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Confusional state
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysarthria
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalitis
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Encephalopathy
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Epilepsy
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hemiparesis
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lethargy
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 179 (1.12%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Melanaemia
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    3 / 179 (1.68%)
    2 / 183 (1.09%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Ascites
         subjects affected / exposed
    1 / 179 (0.56%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    2 / 179 (1.12%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Dysphagia
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric perforation
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 183 (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
    1 / 179 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematochezia
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Intra-abdominal haemorrhage
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Large intestinal obstruction
         subjects affected / exposed
    1 / 179 (0.56%)
    2 / 183 (1.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sialoadenitis
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    1 / 179 (0.56%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct stenosis
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholangitis
         subjects affected / exposed
    0 / 179 (0.00%)
    3 / 183 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic failure
         subjects affected / exposed
    0 / 179 (0.00%)
    3 / 183 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 3
    Hepatitis
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperbilirubinaemia
         subjects affected / exposed
    1 / 179 (0.56%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Hypertransaminasaemia
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oliguria
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pathological fracture
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal abscess
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Genitourinary tract infection
         subjects affected / exposed
    1 / 179 (0.56%)
    3 / 183 (1.64%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Groin abscess
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meningitis bacterial
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia fungal
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 183 (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
    8 / 179 (4.47%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 8
    1 / 1
         deaths causally related to treatment / all
    0 / 3
    1 / 1
    Systemic infection
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyperammonaemia
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Arm A: SoC Arm B: TT
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    147 / 179 (82.12%)
    161 / 183 (87.98%)
    Investigations
    SARS-CoV-2 test positive
         subjects affected / exposed
    8 / 179 (4.47%)
    10 / 183 (5.46%)
         occurrences all number
    9
    10
    Nervous system disorders
    Headache
         subjects affected / exposed
    12 / 179 (6.70%)
    10 / 183 (5.46%)
         occurrences all number
    15
    12
    Paraesthesia
         subjects affected / exposed
    12 / 179 (6.70%)
    8 / 183 (4.37%)
         occurrences all number
    12
    10
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    32 / 179 (17.88%)
    27 / 183 (14.75%)
         occurrences all number
    59
    37
    Neutropenia
         subjects affected / exposed
    24 / 179 (13.41%)
    13 / 183 (7.10%)
         occurrences all number
    72
    25
    Thrombocytopenia
         subjects affected / exposed
    13 / 179 (7.26%)
    14 / 183 (7.65%)
         occurrences all number
    16
    21
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    57 / 179 (31.84%)
    49 / 183 (26.78%)
         occurrences all number
    84
    68
    Fatigue
         subjects affected / exposed
    20 / 179 (11.17%)
    15 / 183 (8.20%)
         occurrences all number
    24
    19
    Mucosal inflammation
         subjects affected / exposed
    23 / 179 (12.85%)
    14 / 183 (7.65%)
         occurrences all number
    32
    18
    Oedema peripheral
         subjects affected / exposed
    9 / 179 (5.03%)
    9 / 183 (4.92%)
         occurrences all number
    10
    9
    Pain
         subjects affected / exposed
    17 / 179 (9.50%)
    16 / 183 (8.74%)
         occurrences all number
    20
    17
    Pyrexia
         subjects affected / exposed
    25 / 179 (13.97%)
    30 / 183 (16.39%)
         occurrences all number
    36
    43
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    14 / 179 (7.82%)
    19 / 183 (10.38%)
         occurrences all number
    18
    20
    Diarrhoea
         subjects affected / exposed
    48 / 179 (26.82%)
    72 / 183 (39.34%)
         occurrences all number
    78
    129
    Vomiting
         subjects affected / exposed
    19 / 179 (10.61%)
    19 / 183 (10.38%)
         occurrences all number
    26
    21
    Abdominal pain
         subjects affected / exposed
    18 / 179 (10.06%)
    16 / 183 (8.74%)
         occurrences all number
    20
    17
    Nausea
         subjects affected / exposed
    43 / 179 (24.02%)
    29 / 183 (15.85%)
         occurrences all number
    74
    41
    Hepatobiliary disorders
    Hypertransaminasaemia
         subjects affected / exposed
    14 / 179 (7.82%)
    10 / 183 (5.46%)
         occurrences all number
    18
    18
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    14 / 179 (7.82%)
    15 / 183 (8.20%)
         occurrences all number
    22
    16
    Dyspnoea
         subjects affected / exposed
    13 / 179 (7.26%)
    8 / 183 (4.37%)
         occurrences all number
    16
    9
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    6 / 179 (3.35%)
    19 / 183 (10.38%)
         occurrences all number
    6
    24
    Rash
         subjects affected / exposed
    16 / 179 (8.94%)
    14 / 183 (7.65%)
         occurrences all number
    23
    18
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    8 / 179 (4.47%)
    11 / 183 (6.01%)
         occurrences all number
    10
    17
    Back pain
         subjects affected / exposed
    7 / 179 (3.91%)
    13 / 183 (7.10%)
         occurrences all number
    7
    14
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    23 / 179 (12.85%)
    21 / 183 (11.48%)
         occurrences all number
    27
    23

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    03 Dec 2020
    The request for a substantial amendment concerns the complete IMPD for the drug entrectinib. The drug supplier, ROCHE, has sent a new Cross Reference Letter indicating the study (Protocol GO40728 – EudraCT 2015-003385-84) to be referenced for this study (Protocol MAR-BAS-18-005 - EudraCT 2018-002190-21). ROCHE has stated that study Protocol GO40728 – EudraCT 2015-003385-84 has already been authorized by AIFA.
    30 Aug 2022
    1. Addition of 5 new IMPs (alpelisib, tepotinib, pralsetinib, talazoparib, selpercatinib) 2. Modification of inclusion criteria no. 5 and no. 8 and modification of exclusion criteria no. 3 3. Modification regarding the use of the drug entrectinib 4. Modification of the timing of sample collection for nanostring analysis and immuno-monitoring 5. Replacement of the centralised laboratory for tissue genomic evaluation 6. Addition of new centralised laboratory for immune-monitoring analysis 7. Additional supply for entrectinib and atezolizumab 8. Update to list of participating centres 9. Update of insurance certificate 10. New company name of the Depo-pack import site 11. Name change of production site: Clinigen Clinical Supplies Management GmBH 12. Update of PI Coordinator’s affiliation
    20 Apr 2023
    The amendment concerns the availability in the study of an additional supply of the medicinal product ipilimumab, which will be available in 50 mg/10 ml vials in addition to that already present in the CTA (200 mg/40 ml).
    14 Feb 2024
    The amendment concerns the availability in the study of an additional supply of the medicine pemigatinib, which will be available in bottles of 14 tablets of 4.5 mg in addition to that already supplied by Incyte (60 tablets of 4.5 mg).

    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.
    Difficulties due to COVID during the study.
    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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