Sarcoma
Conditions
Brief summary
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.
Interventions
DRUGRG1507
Participants will receive R1507 IV infusion as 9 mg/kg once weekly or 27 mg/kg every 3 weeks, depending upon the cohort in which the participants are enrolled.
Sponsors
Sarcoma Alliance for Research through Collaboration
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* progressive, recurrent or refractory Ewing's sarcoma, or recurrent or refractory osteosarcoma, synovial sarcoma, rhabdomyosarcoma, or other sarcomas of the following sub-types: alveolar soft part sarcoma, desmoplastic small round cell tumor, extraskeletal myxoid chondrosarcoma, clear cell sarcoma and myxoid liposarcoma; * Cohort 3 only: age must be \>= 2 and \<= 21 years
Exclusion criteria
* clinically significant unrelated systemic illness which would compromise the participant's ability to tolerate the investigational agent, or interfere with the study procedures or results; * known hypersensitivity to any of the components of R1507 or prior hypersensitivity reactions to monoclonal antibodies; * treatment (within the past 2 weeks) with pharmacologic doses of corticosteroids or other immunosuppressive agents; * current or prior therapy with insulin-like growth factor (IGF) inhibitor (monoclonal or specific kinase inhibitor); * history of solid organ transplant; * other malignant disease diagnosed within the previous 5 years, excluding intra-epithelial cervical neoplasia or non-melanoma skin cancer; * active central nervous system disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Complete or Partial Response, According to World Health Organization (WHO) Criteria in Cohorts 2 to 8 | Baseline up to 6 years (assessed at baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression) | Complete response is the disappearance of all known disease, determined by two consecutive observations not less than 4 weeks apart. Partial response is \>=50% decrease in the total tumor load of the lesions that have been measured to determine the effect of therapy not less than four weeks apart. The observations must be consecutive. |
| Progression-Free Survival (PFS) Rate According to WHO Response Criteria at 18 Weeks From Start of R2607 Treatment in Cohort 1 | Baseline up to 18 weeks (assessed at baseline, every 6 weeks until disease progression) | The PFS survival rate is a landmark analysis of progression-free survival at 18 weeks from start of treatment. Progression-free survival rate at 18 weeks is a dichotomous endpoint, with a patient categorized as alive (with either stable disease or objective response) at 18 weeks from start of treatment. |
| Percentage of Participants With Adverse Events (AEs) in Cohort 1 and 2 | Baseline up to 6 years | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) According to WHO Response Criteria in Cohorts 1 to 8 | Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years) | The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented. Complete response is the disappearance of all known disease, determined by two consecutive observations not less than 4 weeks apart. Partial response is \>=50% decrease in the total tumor load of the lesions that have been measured to determine the effect of therapy not less than four weeks apart. The observations must be consecutive. |
| Time to Progression (TTP) According to WHO Response Criteria in Cohorts 1 to 8 | Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years) | TTP is defined as the time from date of randomization until objective tumor progression. According to the WHO Response Criteria, objective tumor progression is \> 25% increase in the area of one or more measurable lesions or the appearance of new lesions. |
| Failure-Free Survival (FFS) According to WHO Response Criteria in Cohorts 1 to 8 | Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years) | FFS was measured from the date of treatment start to the date of documented disease progression, relapse, or death from any cause. |
| Percentage of Participants With Complete or Partial Response According to WHO Response Criteria in Cohort 1 | Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years) | Complete response is the disappearance of all known disease, determined by two consecutive observations not less than 4 weeks apart. Partial response is \>=50% decrease in the total tumor load of the lesions that have been measured to determine the effect of therapy not less than four weeks apart. The observations must be consecutive. |
| PFS According to WHO Response Criteria in Cohorts 1 to 8 | Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years) | PFS is defined as the duration of time from start of treatment to time of objective progression or death. |
| Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of R1507 | Predose (0 hours [h]), end of 60-90 minutes infusion (EOI), postdose (2, 24, 72-96 h) in Week 1; predose (0 h) and EOI in Weeks 2, 4, 6, 9; predose (0 h), EOI, postdose (48 h) in Week 12; predose (0 h) in Week 13, at final visit (up to 6 years) | — |
| Pharmacokinetics: Clearance (CL) of R1507 | Predose (0 h), EOI (infusion over 60-90 minutes), postdose (2, 24, 72-96 h) in Week 1; predose (0 h) and EOI in Weeks 2, 4, 6, 9; predose (0 h), EOI, postdose (48 h) in Week 12; predose (0 h) in Week 13, at final visit (up to 6 years) | — |
| Overall Survival (OS) in Cohorts 1 to 8 | Baseline until death (up to 6 years) | OS was measured from the time of study registration to the date of death or was censored at the date of last contact. |
| PFS Rate According to WHO Response Criteria at 18 Weeks From Start of R1507 Treatment in Cohorts 2 to 8 | Baseline, every 6 weeks until disease progression (up to 18 weeks) | The PFS survival rate is a landmark analysis of progression-free survival at 18 weeks from start of treatment. Progression-free survival rate at 18 weeks is a dichotomous endpoint, with a patient categorized as alive (with either stable disease or objective response at 18 weeks) from start of treatment. |
| Percentage of Participants With AEs in Cohorts 3-8 | Baseline up to 6 years | — |
Countries
Australia, Canada, France, Germany, Italy, Netherlands, Norway, Spain, Sweden, United Kingdom, United States
Participant flow
Recruitment 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.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Ewings Sarcoma Primary Cohort Participants 2 years of age and older with recurrent or refractory sarcoma receive 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 1 includes individuals with Ewing's sarcoma who have relapsed within 24 weeks after diagnosis and have received two or more prior chemotherapy regimens. | 70 |
| Cohort 2: Ewings Sarcoma Secondary Cohort Participants 2 years of age and older with recurrent or refractory sarcoma receive 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 includes individuals with Ewing's sarcoma who have relapsed more than 24 weeks after diagnosis and have only received one prior chemotherapy regimen. | 54 |
| Cohort 3: Ewings Sarcoma Expanded Cohort Participants 2 to 21 years of age with recurrent or refractory sarcoma receive 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 includes individuals with Ewing's sarcoma who were enrolled and treated following safety evaluation in other cohorts. | 7 |
| Cohort 4: Osteosarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive 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 includes individuals with osteosarcoma. | 40 |
| Cohort 5: Synovial Sarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive 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 includes individuals with synovial sarcoma. | 25 |
| Cohort 6: Rhabdomyosarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive 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 includes individuals with rhabdomyosarcoma. | 41 |
| Cohort 7a: Alveolar Soft Part Sarcoma 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. | 23 |
| Cohort 7b: Desmoplastic Small Round Cell Tumors. Participants 2 years of age and older with recurrent or refractory sarcoma receive 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 includes individuals with desmoplastic small round cell tumors. | 14 |
| Cohort 7c: Extraskeletal Myxoid Chondrosarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive 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 includes individuals with extraskeletal myxoid chondrosarcoma. | 11 |
| Cohort 7d: Clear Cell Sarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive 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 includes individuals with clear cell sarcoma. | 9 |
| Cohort 7e: Myxoid Liposarcoma Participants 2 years of age and older with recurrent or refractory sarcoma receive 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 includes individuals with myxoid liposarcoma. | 12 |
| Cohort 8: Diagnosis Not Specified Participants 2 years of age and older with recurrent or refractory sarcoma receive 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 includes individuals with subtypes of sarcoma not specified in the protocol. | 11 |
| Total | 317 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 1 | 0 | 0 |
| Overall Study | Death | 4 | 0 | 1 | 1 | 2 | 1 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Disease progression | 60 | 50 | 5 | 36 | 23 | 39 | 18 | 12 | 10 | 7 | 12 | 7 |
| Overall Study | Other | 1 | 1 | 1 | 1 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 1 |
| Overall Study | Physician Decision | 3 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Study closed by Sponsor | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 2 | 0 | 0 | 2 | 0 | 1 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Cohort 1: Ewings Sarcoma Primary Cohort | Cohort 2: Ewings Sarcoma Secondary Cohort | Cohort 3: Ewings 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 27 Years STANDARD_DEVIATION 10.72 | 28.3 Years STANDARD_DEVIATION 12.9 | 13.3 Years STANDARD_DEVIATION 3.15 | 33.8 Years STANDARD_DEVIATION 18.83 | 41.7 Years STANDARD_DEVIATION 16.11 | 26.5 Years STANDARD_DEVIATION 12.21 | 31.7 Years STANDARD_DEVIATION 13.67 | 23.1 Years STANDARD_DEVIATION 6.09 | 60.9 Years STANDARD_DEVIATION 11.27 | 26.9 Years STANDARD_DEVIATION 11.01 | 50.6 Years STANDARD_DEVIATION 11.06 | 30.7 Years STANDARD_DEVIATION 18.56 | 31.2 Years STANDARD_DEVIATION 13.36 |
| Sex: Female, Male Female | 20 Participants | 22 Participants | 3 Participants | 20 Participants | 11 Participants | 18 Participants | 12 Participants | 1 Participants | 3 Participants | 2 Participants | 3 Participants | 3 Participants | 118 Participants |
| Sex: Female, Male Male | 50 Participants | 32 Participants | 4 Participants | 20 Participants | 14 Participants | 23 Participants | 11 Participants | 13 Participants | 8 Participants | 7 Participants | 9 Participants | 8 Participants | 199 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 9 / 70 | 5 / 54 | 2 / 7 | 7 / 40 | 3 / 25 | 3 / 41 | 1 / 23 | 0 / 14 | 0 / 11 | 1 / 9 | 1 / 12 | 2 / 11 |
| other Total, other adverse events | 67 / 70 | 52 / 54 | 6 / 7 | 40 / 40 | 25 / 25 | 39 / 41 | 21 / 23 | 12 / 14 | 11 / 11 | 9 / 9 | 12 / 12 | 11 / 11 |
| serious Total, serious adverse events | 11 / 70 | 13 / 54 | 1 / 7 | 4 / 40 | 5 / 25 | 4 / 41 | 1 / 23 | 1 / 14 | 0 / 11 | 3 / 9 | 2 / 12 | 4 / 11 |
Outcome results
Primary
Percentage of Participants With Adverse Events (AEs) in Cohort 1 and 2
Time frame: Baseline up to 6 years
Population: Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Ewings Sarcoma Secondary Cohort | Percentage of Participants With Adverse Events (AEs) in Cohort 1 and 2 | 96 percentage of participants |
| Cohort 3: Ewings Sarcoma Expanded Cohort | Percentage of Participants With Adverse Events (AEs) in Cohort 1 and 2 | 96 percentage of participants |
Primary
Percentage of Participants With Complete or Partial Response, According to World Health Organization (WHO) Criteria in Cohorts 2 to 8
Complete response is the disappearance of all known disease, determined by two consecutive observations not less than 4 weeks apart. Partial response is \>=50% decrease in the total tumor load of the lesions that have been measured to determine the effect of therapy not less than four weeks apart. The observations must be consecutive.
Time frame: Baseline up to 6 years (assessed at baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression)
Population: ITT population included all randomized participants who received at least 1 dose of study drug and had at least 1 post baseline efficacy assessment. There were 0 participants analyzed for Cohort 3 due to no efficacy data being collected for that cohort.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Ewings Sarcoma Secondary Cohort | Percentage of Participants With Complete or Partial Response, According to World Health Organization (WHO) Criteria in Cohorts 2 to 8 | 11.11 Percentage of Participants |
| Cohort 4: Osteosarcoma | Percentage of Participants With Complete or Partial Response, According to World Health Organization (WHO) Criteria in Cohorts 2 to 8 | 2.5 Percentage of Participants |
| Cohort 5: Synovial Sarcoma | Percentage of Participants With Complete or Partial Response, According to World Health Organization (WHO) Criteria in Cohorts 2 to 8 | 4.0 Percentage of Participants |
| Cohort 6: Rhabdomyosarcoma | Percentage of Participants With Complete or Partial Response, According to World Health Organization (WHO) Criteria in Cohorts 2 to 8 | 4.88 Percentage of Participants |
| Cohort 7a: Alveolar Soft Part Sarcoma | Percentage of Participants With Complete or Partial Response, According to World Health Organization (WHO) Criteria in Cohorts 2 to 8 | 0 Percentage of Participants |
| Cohort 7b: Desmoplastic Small Round Cell Tumors. | Percentage of Participants With Complete or Partial Response, According to World Health Organization (WHO) Criteria in Cohorts 2 to 8 | 0 Percentage of Participants |
| Cohort 7c: Extraskeletal Myxoid Chondrosarcoma | Percentage of Participants With Complete or Partial Response, According to World Health Organization (WHO) Criteria in Cohorts 2 to 8 | 0 Percentage of Participants |
| Cohort 7d: Clear Cell Sarcoma | Percentage of Participants With Complete or Partial Response, According to World Health Organization (WHO) Criteria in Cohorts 2 to 8 | 0 Percentage of Participants |
| Cohort 7e: Myxoid Liposarcoma | Percentage of Participants With Complete or Partial Response, According to World Health Organization (WHO) Criteria in Cohorts 2 to 8 | 0 Percentage of Participants |
| Cohort 8: Diagnosis Not Specified | Percentage of Participants With Complete or Partial Response, According to World Health Organization (WHO) Criteria in Cohorts 2 to 8 | 0 Percentage of Participants |
Primary
Progression-Free Survival (PFS) Rate According to WHO Response Criteria at 18 Weeks From Start of R2607 Treatment in Cohort 1
The PFS survival rate is a landmark analysis of progression-free survival at 18 weeks from start of treatment. Progression-free survival rate at 18 weeks is a dichotomous endpoint, with a patient categorized as alive (with either stable disease or objective response) at 18 weeks from start of treatment.
Time frame: Baseline up to 18 weeks (assessed at baseline, every 6 weeks until disease progression)
Population: ITT population included all randomized participants who received at least 1 dose of study drug and had at least 1 post baseline efficacy assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Ewings Sarcoma Secondary Cohort | Progression-Free Survival (PFS) Rate According to WHO Response Criteria at 18 Weeks From Start of R2607 Treatment in Cohort 1 | 15.81 Percentage of Participants |
Secondary
Duration of Response (DOR) According to WHO Response Criteria in Cohorts 1 to 8
The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented. Complete response is the disappearance of all known disease, determined by two consecutive observations not less than 4 weeks apart. Partial response is \>=50% decrease in the total tumor load of the lesions that have been measured to determine the effect of therapy not less than four weeks apart. The observations must be consecutive.
Time frame: Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years)
Population: ITT population included all randomized participants who received at least 1 dose of study drug and had at least 1 post baseline efficacy assessment. There were 0 participants analyzed for Cohort 3, 7 and 8 due to no DOR data being collected for these cohorts.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 2: Ewings Sarcoma Secondary Cohort | Duration of Response (DOR) According to WHO Response Criteria in Cohorts 1 to 8 | 44.29 weeks |
| Cohort 3: Ewings Sarcoma Expanded Cohort | Duration of Response (DOR) According to WHO Response Criteria in Cohorts 1 to 8 | 42.86 weeks |
| Cohort 5: Synovial Sarcoma | Duration of Response (DOR) According to WHO Response Criteria in Cohorts 1 to 8 | NA weeks |
| Cohort 6: Rhabdomyosarcoma | Duration of Response (DOR) According to WHO Response Criteria in Cohorts 1 to 8 | 13.14 weeks |
| Cohort 7a: Alveolar Soft Part Sarcoma | Duration of Response (DOR) According to WHO Response Criteria in Cohorts 1 to 8 | NA weeks |
Secondary
Failure-Free Survival (FFS) According to WHO Response Criteria in Cohorts 1 to 8
FFS was measured from the date of treatment start to the date of documented disease progression, relapse, or death from any cause.
Time frame: Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years)
Population: Data was not collected for this endpoint.
Secondary
Overall Survival (OS) in Cohorts 1 to 8
OS was measured from the time of study registration to the date of death or was censored at the date of last contact.
Time frame: Baseline until death (up to 6 years)
Population: ITT population included all randomized participants who received at least 1 dose of study drug and had at least 1 post baseline efficacy assessment. There were 0 participants analyzed for Cohort 3 and 7c due to no overall survival data being collected for those cohorts.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 2: Ewings Sarcoma Secondary Cohort | Overall Survival (OS) in Cohorts 1 to 8 | 29.57 weeks |
| Cohort 3: Ewings Sarcoma Expanded Cohort | Overall Survival (OS) in Cohorts 1 to 8 | 43.57 weeks |
| Cohort 5: Synovial Sarcoma | Overall Survival (OS) in Cohorts 1 to 8 | 37.14 weeks |
| Cohort 6: Rhabdomyosarcoma | Overall Survival (OS) in Cohorts 1 to 8 | 40.71 weeks |
| Cohort 7a: Alveolar Soft Part Sarcoma | Overall Survival (OS) in Cohorts 1 to 8 | 30.86 weeks |
| Cohort 7b: Desmoplastic Small Round Cell Tumors. | Overall Survival (OS) in Cohorts 1 to 8 | 42.43 weeks |
| Cohort 7c: Extraskeletal Myxoid Chondrosarcoma | Overall Survival (OS) in Cohorts 1 to 8 | 40.86 weeks |
| Cohort 7d: Clear Cell Sarcoma | Overall Survival (OS) in Cohorts 1 to 8 | NA weeks |
| Cohort 7e: Myxoid Liposarcoma | Overall Survival (OS) in Cohorts 1 to 8 | 17.00 weeks |
| Cohort 8: Diagnosis Not Specified | Overall Survival (OS) in Cohorts 1 to 8 | 36.00 weeks |
| Cohort 8: Diagnosis Not Specified | Overall Survival (OS) in Cohorts 1 to 8 | 17.43 weeks |
Secondary
Percentage of Participants With AEs in Cohorts 3-8
Time frame: Baseline up to 6 years
Population: Safety Population: All participants who received at least one dose of study drug at had at least one safety follow-up assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Ewings Sarcoma Secondary Cohort | Percentage of Participants With AEs in Cohorts 3-8 | 85.7 percentage of participants |
| Cohort 3: Ewings Sarcoma Expanded Cohort | Percentage of Participants With AEs in Cohorts 3-8 | 100 percentage of participants |
| Cohort 4: Osteosarcoma | Percentage of Participants With AEs in Cohorts 3-8 | 100 percentage of participants |
| Cohort 5: Synovial Sarcoma | Percentage of Participants With AEs in Cohorts 3-8 | 95 percentage of participants |
| Cohort 6: Rhabdomyosarcoma | Percentage of Participants With AEs in Cohorts 3-8 | 91 percentage of participants |
| Cohort 7a: Alveolar Soft Part Sarcoma | Percentage of Participants With AEs in Cohorts 3-8 | 86 percentage of participants |
| Cohort 7b: Desmoplastic Small Round Cell Tumors. | Percentage of Participants With AEs in Cohorts 3-8 | 100 percentage of participants |
| Cohort 7c: Extraskeletal Myxoid Chondrosarcoma | Percentage of Participants With AEs in Cohorts 3-8 | 100 percentage of participants |
| Cohort 7d: Clear Cell Sarcoma | Percentage of Participants With AEs in Cohorts 3-8 | 100 percentage of participants |
| Cohort 7e: Myxoid Liposarcoma | Percentage of Participants With AEs in Cohorts 3-8 | 100 percentage of participants |
Secondary
Percentage of Participants With Complete or Partial Response According to WHO Response Criteria in Cohort 1
Complete response is the disappearance of all known disease, determined by two consecutive observations not less than 4 weeks apart. Partial response is \>=50% decrease in the total tumor load of the lesions that have been measured to determine the effect of therapy not less than four weeks apart. The observations must be consecutive.
Time frame: Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years)
Population: ITT population included all randomized participants who received at least 1 dose of study drug and had at least 1 post baseline efficacy assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Ewings Sarcoma Secondary Cohort | Percentage of Participants With Complete or Partial Response According to WHO Response Criteria in Cohort 1 | 8.57 percentage of participants |
Secondary
PFS According to WHO Response Criteria in Cohorts 1 to 8
PFS is defined as the duration of time from start of treatment to time of objective progression or death.
Time frame: Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years)
Population: ITT population included all randomized participants who received at least 1 dose of study drug and had at least 1 post baseline efficacy assessment. There were 0 participants analyzed for Cohort 3 due to no efficacy data being collected for that cohort.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 2: Ewings Sarcoma Secondary Cohort | PFS According to WHO Response Criteria in Cohorts 1 to 8 | 6.00 weeks |
| Cohort 3: Ewings Sarcoma Expanded Cohort | PFS According to WHO Response Criteria in Cohorts 1 to 8 | 6.00 weeks |
| Cohort 5: Synovial Sarcoma | PFS According to WHO Response Criteria in Cohorts 1 to 8 | 5.71 weeks |
| Cohort 6: Rhabdomyosarcoma | PFS According to WHO Response Criteria in Cohorts 1 to 8 | 6.00 weeks |
| Cohort 7a: Alveolar Soft Part Sarcoma | PFS According to WHO Response Criteria in Cohorts 1 to 8 | 5.43 weeks |
| Cohort 7b: Desmoplastic Small Round Cell Tumors. | PFS According to WHO Response Criteria in Cohorts 1 to 8 | 11.14 weeks |
| Cohort 7c: Extraskeletal Myxoid Chondrosarcoma | PFS According to WHO Response Criteria in Cohorts 1 to 8 | 6.14 weeks |
| Cohort 7d: Clear Cell Sarcoma | PFS According to WHO Response Criteria in Cohorts 1 to 8 | 18.00 weeks |
| Cohort 7e: Myxoid Liposarcoma | PFS According to WHO Response Criteria in Cohorts 1 to 8 | 5.57 weeks |
| Cohort 8: Diagnosis Not Specified | PFS According to WHO Response Criteria in Cohorts 1 to 8 | 5.86 weeks |
| Cohort 8: Diagnosis Not Specified | PFS According to WHO Response Criteria in Cohorts 1 to 8 | 6.14 weeks |
Secondary
PFS Rate According to WHO Response Criteria at 18 Weeks From Start of R1507 Treatment in Cohorts 2 to 8
The PFS survival rate is a landmark analysis of progression-free survival at 18 weeks from start of treatment. Progression-free survival rate at 18 weeks is a dichotomous endpoint, with a patient categorized as alive (with either stable disease or objective response at 18 weeks) from start of treatment.
Time frame: Baseline, every 6 weeks until disease progression (up to 18 weeks)
Population: ITT population included all randomized participants who received at least 1 dose of study drug and had at least 1 post baseline efficacy assessment. There were 0 participants analyzed for Cohort 3 due to no efficacy data being collected for that cohort.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2: Ewings Sarcoma Secondary Cohort | PFS Rate According to WHO Response Criteria at 18 Weeks From Start of R1507 Treatment in Cohorts 2 to 8 | 17.16 Percentage of Participants |
| Cohort 4: Osteosarcoma | PFS Rate According to WHO Response Criteria at 18 Weeks From Start of R1507 Treatment in Cohorts 2 to 8 | 19.69 Percentage of Participants |
| Cohort 5: Synovial Sarcoma | PFS Rate According to WHO Response Criteria at 18 Weeks From Start of R1507 Treatment in Cohorts 2 to 8 | 4.00 Percentage of Participants |
| Cohort 6: Rhabdomyosarcoma | PFS Rate According to WHO Response Criteria at 18 Weeks From Start of R1507 Treatment in Cohorts 2 to 8 | 7.32 Percentage of Participants |
| Cohort 7a: Alveolar Soft Part Sarcoma | PFS Rate According to WHO Response Criteria at 18 Weeks From Start of R1507 Treatment in Cohorts 2 to 8 | 45.40 Percentage of Participants |
| Cohort 7b: Desmoplastic Small Round Cell Tumors. | PFS Rate According to WHO Response Criteria at 18 Weeks From Start of R1507 Treatment in Cohorts 2 to 8 | 8.16 Percentage of Participants |
| Cohort 7c: Extraskeletal Myxoid Chondrosarcoma | PFS Rate According to WHO Response Criteria at 18 Weeks From Start of R1507 Treatment in Cohorts 2 to 8 | 62.34 Percentage of Participants |
| Cohort 7d: Clear Cell Sarcoma | PFS Rate According to WHO Response Criteria at 18 Weeks From Start of R1507 Treatment in Cohorts 2 to 8 | 0 Percentage of Participants |
| Cohort 7e: Myxoid Liposarcoma | PFS Rate According to WHO Response Criteria at 18 Weeks From Start of R1507 Treatment in Cohorts 2 to 8 | 8.33 Percentage of Participants |
| Cohort 8: Diagnosis Not Specified | PFS Rate According to WHO Response Criteria at 18 Weeks From Start of R1507 Treatment in Cohorts 2 to 8 | 22.86 Percentage of Participants |
Secondary
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of R1507
Time frame: Predose (0 hours [h]), end of 60-90 minutes infusion (EOI), postdose (2, 24, 72-96 h) in Week 1; predose (0 h) and EOI in Weeks 2, 4, 6, 9; predose (0 h), EOI, postdose (48 h) in Week 12; predose (0 h) in Week 13, at final visit (up to 6 years)
Population: Data was not collected for this pharmacokinetic endpoint.
Secondary
Pharmacokinetics: Clearance (CL) of R1507
Time frame: Predose (0 h), EOI (infusion over 60-90 minutes), postdose (2, 24, 72-96 h) in Week 1; predose (0 h) and EOI in Weeks 2, 4, 6, 9; predose (0 h), EOI, postdose (48 h) in Week 12; predose (0 h) in Week 13, at final visit (up to 6 years)
Population: Data was not collected for this pharmacokinetic endpoint.
Secondary
Time to Progression (TTP) According to WHO Response Criteria in Cohorts 1 to 8
TTP is defined as the time from date of randomization until objective tumor progression. According to the WHO Response Criteria, objective tumor progression is \> 25% increase in the area of one or more measurable lesions or the appearance of new lesions.
Time frame: Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years)
Population: ITT population included all randomized participants who received at least 1 dose of study drug and had at least 1 post baseline efficacy assessment. There were 0 participants analyzed for Cohort 3 due to no efficacy data being collected for that cohort.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 2: Ewings Sarcoma Secondary Cohort | Time to Progression (TTP) According to WHO Response Criteria in Cohorts 1 to 8 | 6.00 weeks |
| Cohort 3: Ewings Sarcoma Expanded Cohort | Time to Progression (TTP) According to WHO Response Criteria in Cohorts 1 to 8 | 6.00 weeks |
| Cohort 5: Synovial Sarcoma | Time to Progression (TTP) According to WHO Response Criteria in Cohorts 1 to 8 | 5.71 weeks |
| Cohort 6: Rhabdomyosarcoma | Time to Progression (TTP) According to WHO Response Criteria in Cohorts 1 to 8 | 6.00 weeks |
| Cohort 7a: Alveolar Soft Part Sarcoma | Time to Progression (TTP) According to WHO Response Criteria in Cohorts 1 to 8 | 5.50 weeks |
| Cohort 7b: Desmoplastic Small Round Cell Tumors. | Time to Progression (TTP) According to WHO Response Criteria in Cohorts 1 to 8 | 11.14 weeks |
| Cohort 7c: Extraskeletal Myxoid Chondrosarcoma | Time to Progression (TTP) According to WHO Response Criteria in Cohorts 1 to 8 | 6.14 weeks |
| Cohort 7d: Clear Cell Sarcoma | Time to Progression (TTP) According to WHO Response Criteria in Cohorts 1 to 8 | 18.00 weeks |
| Cohort 7e: Myxoid Liposarcoma | Time to Progression (TTP) According to WHO Response Criteria in Cohorts 1 to 8 | 5.57 weeks |
| Cohort 8: Diagnosis Not Specified | Time to Progression (TTP) According to WHO Response Criteria in Cohorts 1 to 8 | 5.86 weeks |
| Cohort 8: Diagnosis Not Specified | Time to Progression (TTP) According to WHO Response Criteria in Cohorts 1 to 8 | 6.14 weeks |