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    Clinical Trial Results:
    A Phase II Trial of R1507, a Recombinant Human Monoclonal Antibody to the Insulin-Like Growth Factor-1 Receptor for the Treatment of Patients with Recurrent or Refractory Ewing’s Sarcoma, Osteosarcoma, Synovial Sarcoma, Rhabdomyosarcoma and Other Sarcomas

    Summary
    EudraCT number
    		 2007-003940-30
    Trial protocol
    		 GB   DE   FR   ES   SE   NL   IT  
    Global end of trial date
    19 Feb 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    21 Apr 2016
    First version publication date
    21 Apr 2016
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    NO21157
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00642941
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    F. Hoffmann-La Roche AG
    Sponsor organisation address
    Grenzacherstrasse 124, Basel, Switzerland, CH-4070
    Public contact
    Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
    Scientific contact
    Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.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
    19 Feb 2014
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    19 Feb 2014
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The study was primarily designed to determine objective response, progression-free survival (PFS), and the safety and tolerability of R1507 in participants with recurrent or refractory Ewing's sarcoma, osteosarcoma, synovial sarcoma, rhabdomyosarcoma and other sarcomas including alveolar soft part sarcoma, desmoplastic small round cell tumor, extraskeletal myxoid chondrosarcoma, clear cell sarcoma, and myxoid liposarcoma.
    Protection of trial subjects
    The study was conducted in full conformance with the principles of the Declaration of Helsinki, or the laws and regulations of the country in which the research was conducted, whichever afforded greater protection to the participant. The study has fully adhered to the principles outlined in the Guideline for Good Clinical Practice (GCP) International Conference on Harmonisation (ICH) Tripartite Guideline (January 1997) or with local law if it afforded greater protection to the participant. For study sites in the European Union (EU)/European Economic Area (EEA), the study has also complied with the EU Clinical Trial Directive (2001/20/EC). For study sites in the United States (US) or under the US Investigational New Drug application (IND), the study has also adhered to the basic principles of GCP as outlined in the current version of 21 Code of Federal Regulations (CFR), subchapter D, part 312, “Responsibilities of Sponsors and Investigators”; part 50, “Protection of Human Subjects”; and part 56, “Institutional Review Boards”. In other countries where Guidelines for GCP exist, the Sponsor and the investigators have strictly ensured adherence to the stated provision.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    18 Dec 2007
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 6 Years
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Sweden: 5
    Country: Number of subjects enrolled
    United States: 210
    Country: Number of subjects enrolled
    United Kingdom: 12
    Country: Number of subjects enrolled
    Australia: 11
    Country: Number of subjects enrolled
    Canada: 3
    Country: Number of subjects enrolled
    France: 51
    Country: Number of subjects enrolled
    Germany: 15
    Country: Number of subjects enrolled
    Italy: 2
    Country: Number of subjects enrolled
    Netherlands: 3
    Country: Number of subjects enrolled
    Norway: 1
    Country: Number of subjects enrolled
    Spain: 4
    Worldwide total number of subjects
    317
    EEA total number of subjects
    93
    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)
    6
    Adolescents (12-17 years)
    54
    Adults (18-64 years)
    243
    From 65 to 84 years
    13
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 A screening period was included prior to administration of study drug. Tumor scans/X-rays were to be obtained within 4 weeks, fluro-D-glucose positron emission tomography (FDG-PET) scans within 2 weeks, and Baseline laboratory evaluations within 1 week before first dose.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Cohort 1: Ewing's Sarcoma Primary Cohort
    Arm description
    		 Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 milligrams per kilogram (mg/kg) via intravenous (IV) infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 1 included individuals with Ewing's sarcoma who had relapsed within 24 weeks after diagnosis and had received two or more prior chemotherapy regimens.
    Arm type
    		 Experimental

    Investigational medicinal product name
    R1507
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The drug product R1507 was reconstituted and administered via IV infusion as 9 mg/kg once weekly or 27 mg/kg every 3 weeks, depending upon the cohort in which the participant was enrolled.

    Arm title
    		 Cohort 2: Ewing's Sarcoma Secondary Cohort
    Arm description
    		 Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 2 included individuals with Ewing's sarcoma who had relapsed more than 24 weeks after diagnosis or had only received one prior chemotherapy regimen.
    Arm type
    		 Experimental

    Investigational medicinal product name
    R1507
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The drug product R1507 was reconstituted and administered via IV infusion as 9 mg/kg once weekly or 27 mg/kg every 3 weeks, depending upon the cohort in which the participant was enrolled.

    Arm title
    		 Cohort 3: Ewing's Sarcoma Expanded Cohort
    Arm description
    		 Participants 2 to 21 years of age with recurrent or refractory sarcoma received R1507 as 27 mg/kg via IV infusion every 3 weeks until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 3 included individuals with Ewing's sarcoma who were enrolled and treated following safety evaluation in other cohorts.
    Arm type
    		 Experimental

    Investigational medicinal product name
    R1507
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The drug product R1507 was reconstituted and administered via IV infusion as 9 mg/kg once weekly or 27 mg/kg every 3 weeks, depending upon the cohort in which the participant was enrolled.

    Arm title
    		 Cohort 4: Osteosarcoma
    Arm description
    		 Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 4 included individuals with osteosarcoma.
    Arm type
    		 Experimental

    Investigational medicinal product name
    R1507
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The drug product R1507 was reconstituted and administered via IV infusion as 9 mg/kg once weekly or 27 mg/kg every 3 weeks, depending upon the cohort in which the participant was enrolled.

    Arm title
    		 Cohort 5: Synovial Sarcoma
    Arm description
    		 Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 5 included individuals with synovial sarcoma.
    Arm type
    		 Experimental

    Investigational medicinal product name
    R1507
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The drug product R1507 was reconstituted and administered via IV infusion as 9 mg/kg once weekly or 27 mg/kg every 3 weeks, depending upon the cohort in which the participant was enrolled.

    Arm title
    		 Cohort 6: Rhabdomyosarcoma
    Arm description
    		 Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 6 included individuals with rhabdomyosarcoma.
    Arm type
    		 Experimental

    Investigational medicinal product name
    R1507
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The drug product R1507 was reconstituted and administered via IV infusion as 9 mg/kg once weekly or 27 mg/kg every 3 weeks, depending upon the cohort in which the participant was enrolled.

    Arm title
    		 Cohort 7a: Alveolar Soft Part Sarcoma
    Arm description
    		 Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7a included individuals with alveolar soft part sarcoma.
    Arm type
    		 Experimental

    Investigational medicinal product name
    R1507
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The drug product R1507 was reconstituted and administered via IV infusion as 9 mg/kg once weekly or 27 mg/kg every 3 weeks, depending upon the cohort in which the participant was enrolled.

    Arm title
    		 Cohort 7b: Desmoplastic Small Round Cell Tumors
    Arm description
    		 Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7b included individuals with desmoplastic small round cell tumors.
    Arm type
    		 Experimental

    Investigational medicinal product name
    R1507
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The drug product R1507 was reconstituted and administered via IV infusion as 9 mg/kg once weekly or 27 mg/kg every 3 weeks, depending upon the cohort in which the participant was enrolled.

    Arm title
    		 Cohort 7c: Extraskeletal Myxoid Chondrosarcoma
    Arm description
    		 Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7c included individuals with extraskeletal myxoid chondrosarcoma.
    Arm type
    		 Experimental

    Investigational medicinal product name
    R1507
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The drug product R1507 was reconstituted and administered via IV infusion as 9 mg/kg once weekly or 27 mg/kg every 3 weeks, depending upon the cohort in which the participant was enrolled.

    Arm title
    		 Cohort 7d: Clear Cell Sarcoma
    Arm description
    		 Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7d included individuals with clear cell sarcoma.
    Arm type
    		 Experimental

    Investigational medicinal product name
    R1507
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The drug product R1507 was reconstituted and administered via IV infusion as 9 mg/kg once weekly or 27 mg/kg every 3 weeks, depending upon the cohort in which the participant was enrolled.

    Arm title
    		 Cohort 7e: Myxoid Liposarcoma
    Arm description
    		 Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7e included individuals with myxoid liposarcoma.
    Arm type
    		 Experimental

    Investigational medicinal product name
    R1507
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The drug product R1507 was reconstituted and administered via IV infusion as 9 mg/kg once weekly or 27 mg/kg every 3 weeks, depending upon the cohort in which the participant was enrolled.

    Arm title
    		 Cohort 8: Diagnosis Not Specified
    Arm description
    		 Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 8 included individuals with subtypes of sarcoma not specified in the protocol.
    Arm type
    		 Experimental

    Investigational medicinal product name
    R1507
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The drug product R1507 was reconstituted and administered via IV infusion as 9 mg/kg once weekly or 27 mg/kg every 3 weeks, depending upon the cohort in which the participant was enrolled.

    Investigational medicinal product name
    R1507
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    The drug product R1507 was reconstituted and administered via IV infusion as 9 mg/kg once weekly or 27 mg/kg every 3 weeks, depending upon the cohort in which the participant was enrolled.

    Number of subjects in period 1
    		Cohort 1: Ewing's Sarcoma Primary Cohort Cohort 2: Ewing's Sarcoma Secondary Cohort Cohort 3: Ewing's Sarcoma Expanded Cohort Cohort 4: Osteosarcoma Cohort 5: Synovial Sarcoma Cohort 6: Rhabdomyosarcoma Cohort 7a: Alveolar Soft Part Sarcoma Cohort 7b: Desmoplastic Small Round Cell Tumors Cohort 7c: Extraskeletal Myxoid Chondrosarcoma Cohort 7d: Clear Cell Sarcoma Cohort 7e: Myxoid Liposarcoma Cohort 8: Diagnosis Not Specified
    Started
    70
    54
    7
    40
    25
    41
    23
    14
    11
    9
    12
    11
    Completed
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Not completed
    70
    54
    7
    40
    25
    41
    23
    14
    11
    9
    12
    11
         Disease progression
    60
    50
    5
    36
    23
    39
    18
    12
    10
    7
    12
    7
         Protocol violation
    -
    -
    -
    -
    -
    -
    1
    -
    -
    -
    -
    -
         Death
    4
    -
    1
    1
    2
    1
    -
    -
    -
    -
    -
    1
         Not specified
    1
    1
    1
    1
    -
    1
    -
    1
    -
    -
    -
    1
         Refused treatment
    1
    -
    -
    2
    -
    -
    2
    -
    1
    -
    -
    1
         Adverse event
    1
    1
    -
    -
    -
    -
    1
    1
    -
    1
    -
    -
         Investigator decision
    3
    1
    -
    -
    -
    -
    1
    -
    -
    1
    -
    1
         Study closed by Sponsor
    -
    1
    -
    -
    -
    -
    -
    -
    -
    -
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Cohort 1: Ewing's Sarcoma Primary Cohort
    Reporting group description
    		 Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 milligrams per kilogram (mg/kg) via intravenous (IV) infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 1 included individuals with Ewing's sarcoma who had relapsed within 24 weeks after diagnosis and had received two or more prior chemotherapy regimens.

    Reporting group title
    Cohort 2: Ewing's Sarcoma Secondary Cohort
    Reporting group description
    		 Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 2 included individuals with Ewing's sarcoma who had relapsed more than 24 weeks after diagnosis or had only received one prior chemotherapy regimen.

    Reporting group title
    Cohort 3: Ewing's Sarcoma Expanded Cohort
    Reporting group description
    		 Participants 2 to 21 years of age with recurrent or refractory sarcoma received R1507 as 27 mg/kg via IV infusion every 3 weeks until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 3 included individuals with Ewing's sarcoma who were enrolled and treated following safety evaluation in other cohorts.

    Reporting group title
    Cohort 4: Osteosarcoma
    Reporting group description
    		 Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 4 included individuals with osteosarcoma.

    Reporting group title
    Cohort 5: Synovial Sarcoma
    Reporting group description
    		 Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 5 included individuals with synovial sarcoma.

    Reporting group title
    Cohort 6: Rhabdomyosarcoma
    Reporting group description
    		 Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 6 included individuals with rhabdomyosarcoma.

    Reporting group title
    Cohort 7a: Alveolar Soft Part Sarcoma
    Reporting group description
    		 Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7a included individuals with alveolar soft part sarcoma.

    Reporting group title
    Cohort 7b: Desmoplastic Small Round Cell Tumors
    Reporting group description
    		 Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7b included individuals with desmoplastic small round cell tumors.

    Reporting group title
    Cohort 7c: Extraskeletal Myxoid Chondrosarcoma
    Reporting group description
    		 Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7c included individuals with extraskeletal myxoid chondrosarcoma.

    Reporting group title
    Cohort 7d: Clear Cell Sarcoma
    Reporting group description
    		 Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7d included individuals with clear cell sarcoma.

    Reporting group title
    Cohort 7e: Myxoid Liposarcoma
    Reporting group description
    		 Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7e included individuals with myxoid liposarcoma.

    Reporting group title
    Cohort 8: Diagnosis Not Specified
    Reporting group description
    		 Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 8 included individuals with subtypes of sarcoma not specified in the protocol.

    Reporting group values
    		 Cohort 1: Ewing's Sarcoma Primary Cohort Cohort 2: Ewing's Sarcoma Secondary Cohort Cohort 3: Ewing's Sarcoma Expanded Cohort Cohort 4: Osteosarcoma Cohort 5: Synovial Sarcoma Cohort 6: Rhabdomyosarcoma Cohort 7a: Alveolar Soft Part Sarcoma Cohort 7b: Desmoplastic Small Round Cell Tumors Cohort 7c: Extraskeletal Myxoid Chondrosarcoma Cohort 7d: Clear Cell Sarcoma Cohort 7e: Myxoid Liposarcoma Cohort 8: Diagnosis Not Specified Total
    Number of subjects
    		 70 54 7 40 25 41 23 14 11 9 12 11 317
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 27 ( 10.72 ) 28.3 ( 12.29 ) 13.3 ( 3.15 ) 33.8 ( 18.83 ) 41.7 ( 16.11 ) 26.5 ( 12.21 ) 31.7 ( 13.67 ) 23.1 ( 6.09 ) 60.9 ( 11.27 ) 26.9 ( 11.01 ) 50.6 ( 11.06 ) 30.7 ( 18.56 ) -
    Gender categorical
    Units: Subjects
        Female
    		 20 22 3 20 11 18 12 1 3 2 3 3 118
        Male
    		 50 32 4 20 14 23 11 13 8 7 9 8 199

    End points

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    End points reporting groups
    Reporting group title
    Cohort 1: Ewing's Sarcoma Primary Cohort
    Reporting group description
    		 Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 milligrams per kilogram (mg/kg) via intravenous (IV) infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 1 included individuals with Ewing's sarcoma who had relapsed within 24 weeks after diagnosis and had received two or more prior chemotherapy regimens.

    Reporting group title
    Cohort 2: Ewing's Sarcoma Secondary Cohort
    Reporting group description
    		 Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 2 included individuals with Ewing's sarcoma who had relapsed more than 24 weeks after diagnosis or had only received one prior chemotherapy regimen.

    Reporting group title
    Cohort 3: Ewing's Sarcoma Expanded Cohort
    Reporting group description
    		 Participants 2 to 21 years of age with recurrent or refractory sarcoma received R1507 as 27 mg/kg via IV infusion every 3 weeks until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 3 included individuals with Ewing's sarcoma who were enrolled and treated following safety evaluation in other cohorts.

    Reporting group title
    Cohort 4: Osteosarcoma
    Reporting group description
    		 Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 4 included individuals with osteosarcoma.

    Reporting group title
    Cohort 5: Synovial Sarcoma
    Reporting group description
    		 Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 5 included individuals with synovial sarcoma.

    Reporting group title
    Cohort 6: Rhabdomyosarcoma
    Reporting group description
    		 Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 6 included individuals with rhabdomyosarcoma.

    Reporting group title
    Cohort 7a: Alveolar Soft Part Sarcoma
    Reporting group description
    		 Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7a included individuals with alveolar soft part sarcoma.

    Reporting group title
    Cohort 7b: Desmoplastic Small Round Cell Tumors
    Reporting group description
    		 Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7b included individuals with desmoplastic small round cell tumors.

    Reporting group title
    Cohort 7c: Extraskeletal Myxoid Chondrosarcoma
    Reporting group description
    		 Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7c included individuals with extraskeletal myxoid chondrosarcoma.

    Reporting group title
    Cohort 7d: Clear Cell Sarcoma
    Reporting group description
    		 Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7d included individuals with clear cell sarcoma.

    Reporting group title
    Cohort 7e: Myxoid Liposarcoma
    Reporting group description
    		 Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7e included individuals with myxoid liposarcoma.

    Reporting group title
    Cohort 8: Diagnosis Not Specified
    Reporting group description
    		 Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 8 included individuals with subtypes of sarcoma not specified in the protocol.

    Primary: Percentage of Participants with Complete or Partial Response According to World Health Organization (WHO) Response Criteria in Cohorts 2 to 8

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    End point title
    		 Percentage of Participants with Complete or Partial Response According to World Health Organization (WHO) Response Criteria in Cohorts 2 to 8 [1] [2]
    End point description
    Participants were assessed for tumor response according to WHO 1979 criteria. Complete response was defined as disappearance of all known disease, confirmed on two consecutive visits less than (<) 4 weeks apart. Partial response was defined as greater than or equal to (≥) 50 percent (%) decrease in total tumor load on two consecutive visits <4 weeks apart. The percentage of participants with either complete or partial response at any time during the study was to be calculated. All Treated Population: All participants who received at least one dose of study drug.
    End point type
    Primary
    End point timeframe
    Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The data were not analyzed because the development program was terminated by the Sponsor.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The data for Cohort 1 are presented as a separate endpoint.
    End point values
    		 Cohort 2: Ewing's Sarcoma Secondary Cohort Cohort 3: Ewing's Sarcoma Expanded Cohort Cohort 4: Osteosarcoma Cohort 5: Synovial Sarcoma Cohort 6: Rhabdomyosarcoma Cohort 7a: Alveolar Soft Part Sarcoma Cohort 7b: Desmoplastic Small Round Cell Tumors Cohort 7c: Extraskeletal Myxoid Chondrosarcoma Cohort 7d: Clear Cell Sarcoma Cohort 7e: Myxoid Liposarcoma Cohort 8: Diagnosis Not Specified
    Number of subjects analysed
    0 [3]
    0 [4]
    0 [5]
    0 [6]
    0 [7]
    0 [8]
    0 [9]
    0 [10]
    0 [11]
    0 [12]
    0 [13]
    Units: percentage of participants
        number (not applicable)
    Notes
    [3] - The data were not analyzed because the development program was terminated by the Sponsor.
    [4] - The data were not analyzed because the development program was terminated by the Sponsor.
    [5] - The data were not analyzed because the development program was terminated by the Sponsor.
    [6] - The data were not analyzed because the development program was terminated by the Sponsor.
    [7] - The data were not analyzed because the development program was terminated by the Sponsor.
    [8] - The data were not analyzed because the development program was terminated by the Sponsor.
    [9] - The data were not analyzed because the development program was terminated by the Sponsor.
    [10] - The data were not analyzed because the development program was terminated by the Sponsor.
    [11] - The data were not analyzed because the development program was terminated by the Sponsor.
    [12] - The data were not analyzed because the development program was terminated by the Sponsor.
    [13] - The data were not analyzed because the development program was terminated by the Sponsor.
    No statistical analyses for this end point

    Primary: PFS According to WHO Response Criteria at 18 Weeks from Start of R1507 Treatment in Cohort 1

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    End point title
    		 PFS According to WHO Response Criteria at 18 Weeks from Start of R1507 Treatment in Cohort 1 [14] [15]
    End point description
    PFS was defined as the time from start of treatment until first observation of death or disease progression. Progression was defined according to WHO 1979 criteria as ≥25% increase in area of one or more lesions, or the appearance of new lesions. The median duration of PFS at 18 weeks from start of treatment was to be estimated using Kaplan-Meier methodology. All Treated Population.
    End point type
    Primary
    End point timeframe
    Baseline, every 6 weeks until disease progression (up to 18 weeks)
    Notes
    [14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The data were not analyzed because the development program was terminated by the Sponsor.
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The data for Cohorts 2 to 8 are presented as a separate endpoint.
    End point values
    		 Cohort 1: Ewing's Sarcoma Primary Cohort
    Number of subjects analysed
    0 [16]
    Units: months
        median (full range (min-max))
    ( to )
    Notes
    [16] - The data were not analyzed because the development program was terminated by the Sponsor.
    No statistical analyses for this end point

    Secondary: Duration of Response (DOR) According to WHO Response Criteria in Cohorts 2 to 8

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    End point title
    		 Duration of Response (DOR) According to WHO Response Criteria in Cohorts 2 to 8 [17]
    End point description
    DOR was defined as the time from first documented complete or partial response until disease progression. Tumor response was assessed according to WHO 1979 criteria. Complete response was defined as disappearance of all known disease, confirmed on two consecutive visits <4 weeks apart. Partial response was defined as ≥50% decrease in total tumor load on two consecutive visits <4 weeks apart. Progression was defined as ≥25% increase in area of one or more lesions, or the appearance of new lesions. The median duration of DOR was to be estimated using Kaplan-Meier methodology. All Treated Population.
    End point type
    Secondary
    End point timeframe
    Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years)
    Notes
    [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The data for Cohort 1 are presented as a separate endpoint.
    End point values
    		 Cohort 2: Ewing's Sarcoma Secondary Cohort Cohort 3: Ewing's Sarcoma Expanded Cohort Cohort 4: Osteosarcoma Cohort 5: Synovial Sarcoma Cohort 6: Rhabdomyosarcoma Cohort 7a: Alveolar Soft Part Sarcoma Cohort 7b: Desmoplastic Small Round Cell Tumors Cohort 7c: Extraskeletal Myxoid Chondrosarcoma Cohort 7d: Clear Cell Sarcoma Cohort 7e: Myxoid Liposarcoma Cohort 8: Diagnosis Not Specified
    Number of subjects analysed
    0 [18]
    0 [19]
    0 [20]
    0 [21]
    0 [22]
    0 [23]
    0 [24]
    0 [25]
    0 [26]
    0 [27]
    0 [28]
    Units: months
        median (full range (min-max))
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    Notes
    [18] - The data were not analyzed because the development program was terminated by the Sponsor.
    [19] - The data were not analyzed because the development program was terminated by the Sponsor.
    [20] - The data were not analyzed because the development program was terminated by the Sponsor.
    [21] - The data were not analyzed because the development program was terminated by the Sponsor.
    [22] - The data were not analyzed because the development program was terminated by the Sponsor.
    [23] - The data were not analyzed because the development program was terminated by the Sponsor.
    [24] - The data were not analyzed because the development program was terminated by the Sponsor.
    [25] - The data were not analyzed because the development program was terminated by the Sponsor.
    [26] - The data were not analyzed because the development program was terminated by the Sponsor.
    [27] - The data were not analyzed because the development program was terminated by the Sponsor.
    [28] - The data were not analyzed because the development program was terminated by the Sponsor.
    No statistical analyses for this end point

    Secondary: Time to Progression (TTP) According to WHO Response Criteria in Cohorts 2 to 8

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    End point title
    		 Time to Progression (TTP) According to WHO Response Criteria in Cohorts 2 to 8 [29]
    End point description
    TTP was defined as the time from start of treatment until disease progression. Progression was defined according to WHO 1979 criteria as ≥25% increase in area of one or more lesions, or the appearance of new lesions. The median duration of TTP was to be estimated using Kaplan-Meier methodology. All Treated Population.
    End point type
    Secondary
    End point timeframe
    Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years)
    Notes
    [29] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The data for Cohort 1 are presented as a separate endpoint.
    End point values
    		 Cohort 2: Ewing's Sarcoma Secondary Cohort Cohort 3: Ewing's Sarcoma Expanded Cohort Cohort 4: Osteosarcoma Cohort 5: Synovial Sarcoma Cohort 6: Rhabdomyosarcoma Cohort 7a: Alveolar Soft Part Sarcoma Cohort 7b: Desmoplastic Small Round Cell Tumors Cohort 7c: Extraskeletal Myxoid Chondrosarcoma Cohort 7d: Clear Cell Sarcoma Cohort 7e: Myxoid Liposarcoma Cohort 8: Diagnosis Not Specified
    Number of subjects analysed
    0 [30]
    0 [31]
    0 [32]
    0 [33]
    0 [34]
    0 [35]
    0 [36]
    0 [37]
    0 [38]
    0 [39]
    0 [40]
    Units: months
        median (full range (min-max))
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    Notes
    [30] - The data were not analyzed because the development program was terminated by the Sponsor.
    [31] - The data were not analyzed because the development program was terminated by the Sponsor.
    [32] - The data were not analyzed because the development program was terminated by the Sponsor.
    [33] - The data were not analyzed because the development program was terminated by the Sponsor.
    [34] - The data were not analyzed because the development program was terminated by the Sponsor.
    [35] - The data were not analyzed because the development program was terminated by the Sponsor.
    [36] - The data were not analyzed because the development program was terminated by the Sponsor.
    [37] - The data were not analyzed because the development program was terminated by the Sponsor.
    [38] - The data were not analyzed because the development program was terminated by the Sponsor.
    [39] - The data were not analyzed because the development program was terminated by the Sponsor.
    [40] - The data were not analyzed because the development program was terminated by the Sponsor.
    No statistical analyses for this end point

    Secondary: Failure-Free Survival (FFS) According to WHO Response Criteria in Cohorts 2 to 8

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    End point title
    		 Failure-Free Survival (FFS) According to WHO Response Criteria in Cohorts 2 to 8 [41]
    End point description
    Participants were followed for survival status from enrollment until withdrawal from study. FFS was defined as the time from start of treatment until first observation of death or withdrawal from treatment for any reason. The median duration of OS was to be estimated using Kaplan-Meier methodology. All Treated Population.
    End point type
    Secondary
    End point timeframe
    Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years)
    Notes
    [41] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The data for Cohort 1 are presented as a separate endpoint.
    End point values
    		 Cohort 2: Ewing's Sarcoma Secondary Cohort Cohort 3: Ewing's Sarcoma Expanded Cohort Cohort 4: Osteosarcoma Cohort 5: Synovial Sarcoma Cohort 6: Rhabdomyosarcoma Cohort 7a: Alveolar Soft Part Sarcoma Cohort 7b: Desmoplastic Small Round Cell Tumors Cohort 7c: Extraskeletal Myxoid Chondrosarcoma Cohort 7d: Clear Cell Sarcoma Cohort 7e: Myxoid Liposarcoma Cohort 8: Diagnosis Not Specified
    Number of subjects analysed
    0 [42]
    0 [43]
    0 [44]
    0 [45]
    0 [46]
    0 [47]
    0 [48]
    0 [49]
    0 [50]
    0 [51]
    0 [52]
    Units: months
        median (full range (min-max))
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    Notes
    [42] - The data were not analyzed because the development program was terminated by the Sponsor.
    [43] - The data were not analyzed because the development program was terminated by the Sponsor.
    [44] - The data were not analyzed because the development program was terminated by the Sponsor.
    [45] - The data were not analyzed because the development program was terminated by the Sponsor.
    [46] - The data were not analyzed because the development program was terminated by the Sponsor.
    [47] - The data were not analyzed because the development program was terminated by the Sponsor.
    [48] - The data were not analyzed because the development program was terminated by the Sponsor.
    [49] - The data were not analyzed because the development program was terminated by the Sponsor.
    [50] - The data were not analyzed because the development program was terminated by the Sponsor.
    [51] - The data were not analyzed because the development program was terminated by the Sponsor.
    [52] - The data were not analyzed because the development program was terminated by the Sponsor.
    No statistical analyses for this end point

    Secondary: Overall Survival (OS) in Cohorts 2 to 8

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    End point title
    		 Overall Survival (OS) in Cohorts 2 to 8 [53]
    End point description
    Participants were followed for survival status from enrollment until withdrawal from study. OS was defined as the time from start of treatment until death. The median duration of OS was to be estimated using Kaplan-Meier methodology. All Treated Population.
    End point type
    Secondary
    End point timeframe
    Continuously during treatment, then every 12 weeks until withdrawn consent (up to 6 years)
    Notes
    [53] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The data for Cohort 1 are presented as a separate endpoint.
    End point values
    		 Cohort 2: Ewing's Sarcoma Secondary Cohort Cohort 3: Ewing's Sarcoma Expanded Cohort Cohort 4: Osteosarcoma Cohort 5: Synovial Sarcoma Cohort 6: Rhabdomyosarcoma Cohort 7a: Alveolar Soft Part Sarcoma Cohort 7b: Desmoplastic Small Round Cell Tumors Cohort 7c: Extraskeletal Myxoid Chondrosarcoma Cohort 7d: Clear Cell Sarcoma Cohort 7e: Myxoid Liposarcoma Cohort 8: Diagnosis Not Specified
    Number of subjects analysed
    0 [54]
    0 [55]
    0 [56]
    0 [57]
    0 [58]
    0 [59]
    0 [60]
    0 [61]
    0 [62]
    0 [63]
    0 [64]
    Units: months
        median (full range (min-max))
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    Notes
    [54] - The data were not analyzed because the development program was terminated by the Sponsor.
    [55] - The data were not analyzed because the development program was terminated by the Sponsor.
    [56] - The data were not analyzed because the development program was terminated by the Sponsor.
    [57] - The data were not analyzed because the development program was terminated by the Sponsor.
    [58] - The data were not analyzed because the development program was terminated by the Sponsor.
    [59] - The data were not analyzed because the development program was terminated by the Sponsor.
    [60] - The data were not analyzed because the development program was terminated by the Sponsor.
    [61] - The data were not analyzed because the development program was terminated by the Sponsor.
    [62] - The data were not analyzed because the development program was terminated by the Sponsor.
    [63] - The data were not analyzed because the development program was terminated by the Sponsor.
    [64] - The data were not analyzed because the development program was terminated by the Sponsor.
    No statistical analyses for this end point

    Secondary: PFS According to WHO Response Criteria at 18 Weeks from Start of R1507 Treatment in Cohorts 2 to 8

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    End point title
    		 PFS According to WHO Response Criteria at 18 Weeks from Start of R1507 Treatment in Cohorts 2 to 8 [65]
    End point description
    PFS was defined as the time from start of treatment until first observation of death or disease progression. Progression was defined according to WHO 1979 criteria as ≥25% increase in area of one or more lesions, or the appearance of new lesions. The median duration of PFS at 18 weeks from start of treatment was to be estimated using Kaplan-Meier methodology. All Treated Population.
    End point type
    Secondary
    End point timeframe
    Baseline, every 6 weeks until disease progression (up to 18 weeks)
    Notes
    [65] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The data for Cohort 1 are presented as a separate endpoint.
    End point values
    		 Cohort 2: Ewing's Sarcoma Secondary Cohort Cohort 3: Ewing's Sarcoma Expanded Cohort Cohort 4: Osteosarcoma Cohort 5: Synovial Sarcoma Cohort 6: Rhabdomyosarcoma Cohort 7a: Alveolar Soft Part Sarcoma Cohort 7b: Desmoplastic Small Round Cell Tumors Cohort 7c: Extraskeletal Myxoid Chondrosarcoma Cohort 7d: Clear Cell Sarcoma Cohort 7e: Myxoid Liposarcoma Cohort 8: Diagnosis Not Specified
    Number of subjects analysed
    0 [66]
    0 [67]
    0 [68]
    0 [69]
    0 [70]
    0 [71]
    0 [72]
    0 [73]
    0 [74]
    0 [75]
    0 [76]
    Units: months
        median (full range (min-max))
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    Notes
    [66] - The data were not analyzed because the development program was terminated by the Sponsor.
    [67] - The data were not analyzed because the development program was terminated by the Sponsor.
    [68] - The data were not analyzed because the development program was terminated by the Sponsor.
    [69] - The data were not analyzed because the development program was terminated by the Sponsor.
    [70] - The data were not analyzed because the development program was terminated by the Sponsor.
    [71] - The data were not analyzed because the development program was terminated by the Sponsor.
    [72] - The data were not analyzed because the development program was terminated by the Sponsor.
    [73] - The data were not analyzed because the development program was terminated by the Sponsor.
    [74] - The data were not analyzed because the development program was terminated by the Sponsor.
    [75] - The data were not analyzed because the development program was terminated by the Sponsor.
    [76] - The data were not analyzed because the development program was terminated by the Sponsor.
    No statistical analyses for this end point

    Secondary: PFS According to WHO Response Criteria in Cohorts 2 to 8

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    End point title
    		 PFS According to WHO Response Criteria in Cohorts 2 to 8 [77]
    End point description
    PFS was defined as the time from start of treatment until first observation of death or disease progression. Progression was defined according to WHO 1979 criteria as ≥25% increase in area of one or more lesions, or the appearance of new lesions. The median duration of PFS was to be estimated using Kaplan-Meier methodology. All Treated Population.
    End point type
    Secondary
    End point timeframe
    Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years)
    Notes
    [77] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The data for Cohort 1 are presented as a separate endpoint.
    End point values
    		 Cohort 2: Ewing's Sarcoma Secondary Cohort Cohort 3: Ewing's Sarcoma Expanded Cohort Cohort 4: Osteosarcoma Cohort 5: Synovial Sarcoma Cohort 6: Rhabdomyosarcoma Cohort 7a: Alveolar Soft Part Sarcoma Cohort 7b: Desmoplastic Small Round Cell Tumors Cohort 7c: Extraskeletal Myxoid Chondrosarcoma Cohort 7d: Clear Cell Sarcoma Cohort 7e: Myxoid Liposarcoma Cohort 8: Diagnosis Not Specified
    Number of subjects analysed
    0 [78]
    0 [79]
    0 [80]
    0 [81]
    0 [82]
    0 [83]
    0 [84]
    0 [85]
    0 [86]
    0 [87]
    0 [88]
    Units: months
        median (full range (min-max))
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    Notes
    [78] - The data were not analyzed because the development program was terminated by the Sponsor.
    [79] - The data were not analyzed because the development program was terminated by the Sponsor.
    [80] - The data were not analyzed because the development program was terminated by the Sponsor.
    [81] - The data were not analyzed because the development program was terminated by the Sponsor.
    [82] - The data were not analyzed because the development program was terminated by the Sponsor.
    [83] - The data were not analyzed because the development program was terminated by the Sponsor.
    [84] - The data were not analyzed because the development program was terminated by the Sponsor.
    [85] - The data were not analyzed because the development program was terminated by the Sponsor.
    [86] - The data were not analyzed because the development program was terminated by the Sponsor.
    [87] - The data were not analyzed because the development program was terminated by the Sponsor.
    [88] - The data were not analyzed because the development program was terminated by the Sponsor.
    No statistical analyses for this end point

    Secondary: Percentage of Participants with Complete or Partial Response According to WHO Response Criteria in Cohort 1

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    End point title
    		 Percentage of Participants with Complete or Partial Response According to WHO Response Criteria in Cohort 1 [89]
    End point description
    Participants were assessed for tumor response according to WHO 1979 criteria. Complete response was defined as disappearance of all known disease, confirmed on two consecutive visits <4 weeks apart. Partial response was defined as ≥50% decrease in total tumor load on two consecutive visits <4 weeks apart. The percentage of participants with either complete or partial response at any time during the study was calculated. All Treated Population.
    End point type
    Secondary
    End point timeframe
    Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years)
    Notes
    [89] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The data for Cohorts 2 to 8 are presented as a separate endpoint.
    End point values
    		 Cohort 1: Ewing's Sarcoma Primary Cohort
    Number of subjects analysed
    0 [90]
    Units: percentage of participants
        number (not applicable)
    Notes
    [90] - The data were not analyzed because the development program was terminated by the Sponsor.
    No statistical analyses for this end point

    Secondary: TTP According to WHO Response Criteria in Cohort 1

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    End point title
    		 TTP According to WHO Response Criteria in Cohort 1 [91]
    End point description
    TTP was defined as the time from start of treatment until disease progression. Progression was defined according to WHO 1979 criteria as ≥25% increase in area of one or more lesions, or the appearance of new lesions. The median duration of TTP was to be estimated using Kaplan-Meier methodology. All Treated Population.
    End point type
    Secondary
    End point timeframe
    Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years)
    Notes
    [91] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The data for Cohorts 2 to 8 are presented as a separate endpoint.
    End point values
    		 Cohort 1: Ewing's Sarcoma Primary Cohort
    Number of subjects analysed
    0 [92]
    Units: months
        median (full range (min-max))
    ( to )
    Notes
    [92] - The data were not analyzed because the development program was terminated by the Sponsor.
    No statistical analyses for this end point

    Secondary: FFS According to WHO Response Criteria in Cohort 1

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    End point title
    		 FFS According to WHO Response Criteria in Cohort 1 [93]
    End point description
    Participants were followed for survival status from enrollment until withdrawal from study. FFS was defined as the time from start of treatment until first observation of death or withdrawal from treatment for any reason. The median duration of OS was to be estimated using Kaplan-Meier methodology. All Treated Population.
    End point type
    Secondary
    End point timeframe
    Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years)
    Notes
    [93] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The data for Cohorts 2 to 8 are presented as a separate endpoint.
    End point values
    		 Cohort 1: Ewing's Sarcoma Primary Cohort
    Number of subjects analysed
    0 [94]
    Units: months
        median (full range (min-max))
    ( to )
    Notes
    [94] - The data were not analyzed because the development program was terminated by the Sponsor.
    No statistical analyses for this end point

    Secondary: DOR According to WHO Response Criteria in Cohort 1

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    End point title
    		 DOR According to WHO Response Criteria in Cohort 1 [95]
    End point description
    DOR was defined as the time from first documented complete or partial response until disease progression. Tumor response was assessed according to WHO 1979 criteria. Complete response was defined as disappearance of all known disease, confirmed on two consecutive visits <4 weeks apart. Partial response was defined as ≥50% decrease in total tumor load on two consecutive visits <4 weeks apart. Progression was defined as ≥25% increase in area of one or more lesions, or the appearance of new lesions. The median duration of DOR was to be estimated using Kaplan-Meier methodology. All Treated Population.
    End point type
    Secondary
    End point timeframe
    Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years)
    Notes
    [95] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The data for Cohorts 2 to 8 are presented as a separate endpoint.
    End point values
    		 Cohort 1: Ewing's Sarcoma Primary Cohort
    Number of subjects analysed
    0 [96]
    Units: months
        median (full range (min-max))
    ( to )
    Notes
    [96] - The data were not analyzed because the development program was terminated by the Sponsor.
    No statistical analyses for this end point

    Secondary: PFS According to WHO Response Criteria in Cohort 1

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    End point title
    		 PFS According to WHO Response Criteria in Cohort 1 [97]
    End point description
    PFS was defined as the time from start of treatment until first observation of death or disease progression. Progression was defined according to WHO 1979 criteria as ≥25% increase in area of one or more lesions, or the appearance of new lesions. The median duration of PFS was to be estimated using Kaplan-Meier methodology. All Treated Population.
    End point type
    Secondary
    End point timeframe
    Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years)
    Notes
    [97] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The data for Cohorts 2 to 8 are presented as a separate endpoint.
    End point values
    		 Cohort 1: Ewing's Sarcoma Primary Cohort
    Number of subjects analysed
    0 [98]
    Units: months
        median (full range (min-max))
    ( to )
    Notes
    [98] - The data were not analyzed because the development program was terminated by the Sponsor.
    No statistical analyses for this end point

    Secondary: OS in Cohort 1

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    End point title
    		 OS in Cohort 1 [99]
    End point description
    Participants were followed for survival status from enrollment until withdrawal from study. OS was defined as the time from start of treatment until death. The median duration of OS was to be estimated using Kaplan-Meier methodology. All Treated Population.
    End point type
    Secondary
    End point timeframe
    Continuously during treatment, then every 12 weeks until withdrawn consent (up to 6 years)
    Notes
    [99] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The data for Cohorts 2 to 8 are presented as a separate endpoint.
    End point values
    		 Cohort 1: Ewing's Sarcoma Primary Cohort
    Number of subjects analysed
    0 [100]
    Units: months
        median (full range (min-max))
    ( to )
    Notes
    [100] - The data were not analyzed because the development program was terminated by the Sponsor.
    No statistical analyses for this end point

    Secondary: Area Under the Concentration-Time Curve of R1507

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    End point title
    		 Area Under the Concentration-Time Curve of R1507
    End point description
    Serum samples were obtained at various timepoints to assessed the pharmacokinetic profile of R1507. (The Ewing's Sarcoma Expanded Cohort provided additional samples in Weeks 3, 7, 10, and up to 30 days after last dose. Additionally, sampling was optional for participants <18 years of age.) The area under the concentration-time curve was to be calculated and averaged among all participants and expressed in hours by micrograms per milliliter (h*μg/mL). All Treated Population.
    End point type
    Secondary
    End point timeframe
    Pre-dose (0 hours [h]), end of infusion (EOI), post-dose (2, 24, 72-96 h) in Week 1; pre-dose (0 h) and EOI in Weeks 2, 4, 6, 9; pre-dose (0 h), EOI, post-dose (48 h) in Week 12; pre-dose (0 h) in Week 13, and at time of final visit (up to 6 years)
    End point values
    		 Cohort 1: Ewing's Sarcoma Primary Cohort Cohort 2: Ewing's Sarcoma Secondary Cohort Cohort 3: Ewing's Sarcoma Expanded Cohort Cohort 4: Osteosarcoma Cohort 5: Synovial Sarcoma Cohort 6: Rhabdomyosarcoma Cohort 7a: Alveolar Soft Part Sarcoma Cohort 7b: Desmoplastic Small Round Cell Tumors Cohort 7c: Extraskeletal Myxoid Chondrosarcoma Cohort 7d: Clear Cell Sarcoma Cohort 7e: Myxoid Liposarcoma Cohort 8: Diagnosis Not Specified
    Number of subjects analysed
    0 [101]
    0 [102]
    0 [103]
    0 [104]
    0 [105]
    0 [106]
    0 [107]
    0 [108]
    0 [109]
    0 [110]
    0 [111]
    0 [112]
    Units: h*μg/mL
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    Notes
    [101] - The data were not analyzed because the development program was terminated by the Sponsor.
    [102] - The data were not analyzed because the development program was terminated by the Sponsor.
    [103] - The data were not analyzed because the development program was terminated by the Sponsor.
    [104] - The data were not analyzed because the development program was terminated by the Sponsor.
    [105] - The data were not analyzed because the development program was terminated by the Sponsor.
    [106] - The data were not analyzed because the development program was terminated by the Sponsor.
    [107] - The data were not analyzed because the development program was terminated by the Sponsor.
    [108] - The data were not analyzed because the development program was terminated by the Sponsor.
    [109] - The data were not analyzed because the development program was terminated by the Sponsor.
    [110] - The data were not analyzed because the development program was terminated by the Sponsor.
    [111] - The data were not analyzed because the development program was terminated by the Sponsor.
    [112] - The data were not analyzed because the development program was terminated by the Sponsor.
    No statistical analyses for this end point

    Secondary: Clearance of R1507

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    End point title
    		 Clearance of R1507
    End point description
    Serum samples were obtained at various timepoints to assessed the pharmacokinetic profile of R1507. (The Ewing's Sarcoma Expanded Cohort provided additional samples in Weeks 3, 7, 10, and up to 30 days after last dose. Additionally, sampling was optional for participants <18 years of age.) The maximum observed concentration across all observations was to be averaged among all participants. All Treated Population.
    End point type
    Secondary
    End point timeframe
    Pre-dose (0 h), EOI, post-dose (2, 24, 72-96 h) in Week 1; pre-dose (0 h) and EOI in Weeks 2, 4, 6, 9; pre-dose (0 h), EOI, post-dose (48 h) in Week 12; pre-dose (0 h) in Week 13, and at time of final visit (up to 6 years)
    End point values
    		 Cohort 1: Ewing's Sarcoma Primary Cohort Cohort 2: Ewing's Sarcoma Secondary Cohort Cohort 3: Ewing's Sarcoma Expanded Cohort Cohort 4: Osteosarcoma Cohort 5: Synovial Sarcoma Cohort 6: Rhabdomyosarcoma Cohort 7a: Alveolar Soft Part Sarcoma Cohort 7b: Desmoplastic Small Round Cell Tumors Cohort 7c: Extraskeletal Myxoid Chondrosarcoma Cohort 7d: Clear Cell Sarcoma Cohort 7e: Myxoid Liposarcoma Cohort 8: Diagnosis Not Specified
    Number of subjects analysed
    0 [113]
    0 [114]
    0 [115]
    0 [116]
    0 [117]
    0 [118]
    0 [119]
    0 [120]
    0 [121]
    0 [122]
    0 [123]
    0 [124]
    Units: mL/day
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    Notes
    [113] - The data were not analyzed because the development program was terminated by the Sponsor.
    [114] - The data were not analyzed because the development program was terminated by the Sponsor.
    [115] - The data were not analyzed because the development program was terminated by the Sponsor.
    [116] - The data were not analyzed because the development program was terminated by the Sponsor.
    [117] - The data were not analyzed because the development program was terminated by the Sponsor.
    [118] - The data were not analyzed because the development program was terminated by the Sponsor.
    [119] - The data were not analyzed because the development program was terminated by the Sponsor.
    [120] - The data were not analyzed because the development program was terminated by the Sponsor.
    [121] - The data were not analyzed because the development program was terminated by the Sponsor.
    [122] - The data were not analyzed because the development program was terminated by the Sponsor.
    [123] - The data were not analyzed because the development program was terminated by the Sponsor.
    [124] - The data were not analyzed because the development program was terminated by the Sponsor.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Continuously during treatment and approximately 7 days after discontinuation (up to 24 weeks)
    Adverse event reporting additional description
    Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.1
    Reporting groups
    Reporting group title
    All Cohorts
    Reporting group description
    		 Participants 2 years of age and older with recurrent or refractory sarcoma received R1507 via IV infusion as 9 mg/kg once weekly or 27 mg/kg every 3 weeks until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death.

    Serious adverse events
    		 All Cohorts
    Total subjects affected by serious adverse events
         subjects affected / exposed
    49 / 317 (15.46%)
         number of deaths (all causes)
    34
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour haemorrhage
         subjects affected / exposed
    1 / 317 (0.32%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    1 / 317 (0.32%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Haemorrhage
         subjects affected / exposed
    1 / 317 (0.32%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    1 / 317 (0.32%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Thrombosis
         subjects affected / exposed
    1 / 317 (0.32%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    1 / 317 (0.32%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    Inflammation
         subjects affected / exposed
    1 / 317 (0.32%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    1 / 317 (0.32%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pain
         subjects affected / exposed
    2 / 317 (0.63%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 317 (0.32%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    1 / 317 (0.32%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Dyspnoea
         subjects affected / exposed
    1 / 317 (0.32%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hypoxia
         subjects affected / exposed
    1 / 317 (0.32%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pleural effusion
         subjects affected / exposed
    2 / 317 (0.63%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    Pneumothorax
         subjects affected / exposed
    1 / 317 (0.32%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    2 / 317 (0.63%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 317 (0.32%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Psychiatric disorders
    Mental status changes
         subjects affected / exposed
    1 / 317 (0.32%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Injury, poisoning and procedural complications
    Spinal compression fracture
         subjects affected / exposed
    1 / 317 (0.32%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nervous system disorders
    Facial palsy
         subjects affected / exposed
    1 / 317 (0.32%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Somnolence
         subjects affected / exposed
    3 / 317 (0.95%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Blood and lymphatic system disorders
    Thrombocytopenia
         subjects affected / exposed
    1 / 317 (0.32%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    2 / 317 (0.63%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Intestinal perforation
         subjects affected / exposed
    1 / 317 (0.32%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 317 (0.32%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Obstruction gastric
         subjects affected / exposed
    1 / 317 (0.32%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 317 (0.32%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vomiting
         subjects affected / exposed
    2 / 317 (0.63%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    Renal and urinary disorders
    Hydronephrosis
         subjects affected / exposed
    1 / 317 (0.32%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Endocrine disorders
    Adrenal haemorrhage
         subjects affected / exposed
    1 / 317 (0.32%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 317 (0.32%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Flank pain
         subjects affected / exposed
    1 / 317 (0.32%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Neck pain
         subjects affected / exposed
    1 / 317 (0.32%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pain in extremity
         subjects affected / exposed
    1 / 317 (0.32%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    2 / 317 (0.63%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    Bacteraemia
         subjects affected / exposed
    1 / 317 (0.32%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 317 (0.32%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Device related infection
         subjects affected / exposed
    2 / 317 (0.63%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Escherichia sepsis
         subjects affected / exposed
    1 / 317 (0.32%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infection
         subjects affected / exposed
    3 / 317 (0.95%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 317 (0.32%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 317 (0.32%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    1 / 317 (0.32%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 317 (0.32%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    2 / 317 (0.63%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    1 / 317 (0.32%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 317 (0.32%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 All Cohorts
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    277 / 317 (87.38%)
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    26 / 317 (8.20%)
         occurrences all number
    36
    Aspartate aminotransferase increased
         subjects affected / exposed
    32 / 317 (10.09%)
         occurrences all number
    46
    Blood alkaline phosphatase increased
         subjects affected / exposed
    22 / 317 (6.94%)
         occurrences all number
    24
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    17 / 317 (5.36%)
         occurrences all number
    17
    Weight decreased
         subjects affected / exposed
    37 / 317 (11.67%)
         occurrences all number
    37
    Nervous system disorders
    Headache
         subjects affected / exposed
    53 / 317 (16.72%)
         occurrences all number
    80
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    31 / 317 (9.78%)
         occurrences all number
    39
    Thrombocytopenia
         subjects affected / exposed
    20 / 317 (6.31%)
         occurrences all number
    26
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    27 / 317 (8.52%)
         occurrences all number
    40
    Chest pain
         subjects affected / exposed
    30 / 317 (9.46%)
         occurrences all number
    40
    Fatigue
         subjects affected / exposed
    100 / 317 (31.55%)
         occurrences all number
    121
    Infusion related reaction
         subjects affected / exposed
    18 / 317 (5.68%)
         occurrences all number
    22
    Pain
         subjects affected / exposed
    28 / 317 (8.83%)
         occurrences all number
    39
    Pyrexia
         subjects affected / exposed
    41 / 317 (12.93%)
         occurrences all number
    52
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    21 / 317 (6.62%)
         occurrences all number
    26
    Constipation
         subjects affected / exposed
    49 / 317 (15.46%)
         occurrences all number
    53
    Diarrhoea
         subjects affected / exposed
    56 / 317 (17.67%)
         occurrences all number
    99
    Nausea
         subjects affected / exposed
    70 / 317 (22.08%)
         occurrences all number
    104
    Vomiting
         subjects affected / exposed
    55 / 317 (17.35%)
         occurrences all number
    86
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    51 / 317 (16.09%)
         occurrences all number
    62
    Dyspnoea
         subjects affected / exposed
    38 / 317 (11.99%)
         occurrences all number
    41
    Epistaxis
         subjects affected / exposed
    21 / 317 (6.62%)
         occurrences all number
    25
    Oropharyngeal pain
         subjects affected / exposed
    20 / 317 (6.31%)
         occurrences all number
    30
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    18 / 317 (5.68%)
         occurrences all number
    18
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    22 / 317 (6.94%)
         occurrences all number
    22
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    24 / 317 (7.57%)
         occurrences all number
    29
    Back pain
         subjects affected / exposed
    37 / 317 (11.67%)
         occurrences all number
    51
    Muscle spasms
         subjects affected / exposed
    43 / 317 (13.56%)
         occurrences all number
    53
    Musculoskeletal pain
         subjects affected / exposed
    27 / 317 (8.52%)
         occurrences all number
    30
    Pain in extremity
         subjects affected / exposed
    24 / 317 (7.57%)
         occurrences all number
    29
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    47 / 317 (14.83%)
         occurrences all number
    53
    Hyperglycaemia
         subjects affected / exposed
    48 / 317 (15.14%)
         occurrences all number
    76
    Hypoalbuminaemia
         subjects affected / exposed
    18 / 317 (5.68%)
         occurrences all number
    21
    Hypokalaemia
         subjects affected / exposed
    18 / 317 (5.68%)
         occurrences all number
    24
    Hyponatraemia
         subjects affected / exposed
    22 / 317 (6.94%)
         occurrences all number
    25
    Hypophosphataemia
         subjects affected / exposed
    18 / 317 (5.68%)
         occurrences all number
    21

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    09 Nov 2007
    The protocol was amended for administrative changes and minor clarifications, as well as updates to the timing of assessments. Blood sampling was made optional for participants <18 years of age. A statistical analysis plan was also added for pharmacokinetic endpoints.
    01 Aug 2008
    The protocol amendment was released to clarify the cohorts/study design, including the planned interim analysis for the Ewing's Sarcoma Primary Cohort. Secondary endpoints for TTP, FFS, and OS were also added. The minimum eligible age was changed from 12 years to 2 years. Among several other clarifications and formatting updates, the infusion time of R1507 was specified.
    09 Jul 2009
    The final protocol amendment added the Ewing's Sarcoma Expanded Cohort to allow testing of R1507 in a 3-week dosing schedule. Additional updates were made to accommodate the new cohort, including a special pharmacokinetic sampling schedule. The post-infusion monitoring time was also shortened on the basis of favorable tolerability in other clinical studies of R1507.

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    19 Feb 2014
    The last dose of study drug was received, after which the study was closed by the Sponsor on the basis of decisions to discontinue further development of R1507. The decision was not due to safety concerns.
    -

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    The study was closed to further enrollment due to a decision by the Sponsor to discontinue development of R1507. The decision was made based upon available data from other completed/ongoing trials of R1507 and was not due to safety concerns.
    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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