Trial Outcomes & Findings for A Study to Determine the Activity of Robatumumab (SCH 717454) in Participants With Relapsed Osteosarcoma or Ewing's Sarcoma (MK-7454-002/P04720) (NCT NCT00617890)

Last Updated: 2018-08-23

Results Overview

This is a measure of the number of participants with a complete response (CR) or partial response (PR) to therapy, confirmed by central review. Response was based on Response Evaluation Criteria in Solid Tumors (RECIST) and World Health Organization (WHO) criteria.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

219 participants

Primary outcome timeframe

Up to 1 year following the start of study therapy

Results posted on

2018-08-23

Participant Flow

Participant milestones

Participant milestones
Measure	Group 1: 0.3 mg/kg Participants received robatumumab 0.3 mg/kg intravenously (IV) as a single dose on Day 1, followed by surgery on Day 10 to 14, and four weeks later, resumption of robatumumab 0.3 mg/kg on the same calendar day (± 3 days) once every 2 weeks until disease recurrence or up to 1 year of dosing. This group comprised participants with resectable osteosarcoma that relapsed within 6 months of prior definitive treatment (eg surgical metastasectomy) and having at least one prior chemotherapy regimen containing a platinum agent and doxorubicin.	Group 1: 10 mg/kg Participants received robatumumab 10 mg/kg IV as a single dose on Day 1, followed by surgery on Day 10 to 14, and four weeks later, resumption of robatumumab 10 mg/kg on the same calendar day (± 3 days) once every 2 weeks until disease recurrence or up to 1 year of dosing. This group comprised participants with resectable osteosarcoma that relapsed within 6 months of prior definitive treatment (eg surgical metastasectomy) and having at least one prior chemotherapy regimen containing a platinum agent and doxorubicin.	Group 2: 10 mg/kg Participants received robatumumab 10 mg/kg IV biweekly until disease recurrence or up to 1 year of dosing. This group comprised participants with relapsed and unresectable osteosarcoma refractory to prior chemotherapy with a platinum- and doxorubicin-containing regimen.	Group 3: 10 mg/kg Participants received robatumumab 10 mg/kg IV biweekly until disease recurrence or up to 1 year of dosing. This group comprised participants with Ewing's sarcoma refractory to prior treatment with at least 3 of the following agents: ifosfamide, etoposide, cyclophosphamide, doxorubicin, or vincristine.
Overall Study STARTED	35	33	35	116
Overall Study Received Treatment	34	33	34	115
Overall Study COMPLETED	4	5	0	1
Overall Study NOT COMPLETED	31	28	35	115

Reasons for withdrawal

Reasons for withdrawal
Measure	Group 1: 0.3 mg/kg Participants received robatumumab 0.3 mg/kg intravenously (IV) as a single dose on Day 1, followed by surgery on Day 10 to 14, and four weeks later, resumption of robatumumab 0.3 mg/kg on the same calendar day (± 3 days) once every 2 weeks until disease recurrence or up to 1 year of dosing. This group comprised participants with resectable osteosarcoma that relapsed within 6 months of prior definitive treatment (eg surgical metastasectomy) and having at least one prior chemotherapy regimen containing a platinum agent and doxorubicin.	Group 1: 10 mg/kg Participants received robatumumab 10 mg/kg IV as a single dose on Day 1, followed by surgery on Day 10 to 14, and four weeks later, resumption of robatumumab 10 mg/kg on the same calendar day (± 3 days) once every 2 weeks until disease recurrence or up to 1 year of dosing. This group comprised participants with resectable osteosarcoma that relapsed within 6 months of prior definitive treatment (eg surgical metastasectomy) and having at least one prior chemotherapy regimen containing a platinum agent and doxorubicin.	Group 2: 10 mg/kg Participants received robatumumab 10 mg/kg IV biweekly until disease recurrence or up to 1 year of dosing. This group comprised participants with relapsed and unresectable osteosarcoma refractory to prior chemotherapy with a platinum- and doxorubicin-containing regimen.	Group 3: 10 mg/kg Participants received robatumumab 10 mg/kg IV biweekly until disease recurrence or up to 1 year of dosing. This group comprised participants with Ewing's sarcoma refractory to prior treatment with at least 3 of the following agents: ifosfamide, etoposide, cyclophosphamide, doxorubicin, or vincristine.
Overall Study Treatment ongoing at data cut-off	0	0	0	5
Overall Study Lack of Efficacy	23	26	30	97
Overall Study Lost to Follow-up	0	0	1	2
Overall Study Withdrawal by Subject	4	1	0	2
Overall Study Protocol Violation	2	1	0	0
Overall Study Adverse Event	1	0	3	8
Overall Study Not treated	1	0	1	1

Baseline Characteristics

A Study to Determine the Activity of Robatumumab (SCH 717454) in Participants With Relapsed Osteosarcoma or Ewing's Sarcoma (MK-7454-002/P04720)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group 1: 0.3 mg/kg n=35 Participants Participants received robatumumab 0.3 mg/kg intravenously (IV) as a single dose on Day 1, followed by surgery on Day 10 to 14, and four weeks later, resumption of robatumumab 0.3 mg/kg on the same calendar day (± 3 days) once every 2 weeks until disease recurrence or up to 1 year of dosing. This group comprised participants with resectable osteosarcoma that relapsed within 6 months of prior definitive treatment (eg surgical metastasectomy) and having at least one prior chemotherapy regimen containing a platinum agent and doxorubicin.	Group 1: 10 mg/kg n=33 Participants Participants received robatumumab 10 mg/kg IV as a single dose on Day 1, followed by surgery on Day 10 to 14, and four weeks later, resumption of robatumumab 10 mg/kg on the same calendar day (± 3 days) once every 2 weeks until disease recurrence or up to 1 year of dosing. This group comprised participants with resectable osteosarcoma that relapsed within 6 months of prior definitive treatment (eg surgical metastasectomy) and having at least one prior chemotherapy regimen containing a platinum agent and doxorubicin.	Group 2: 10 mg/kg n=35 Participants Participants received robatumumab 10 mg/kg IV biweekly until disease recurrence or up to 1 year of dosing. This group comprised participants with relapsed and unresectable osteosarcoma refractory to prior chemotherapy with a platinum- and doxorubicin-containing regimen.	Group 3: 10 mg/kg n=116 Participants Participants received robatumumab 10 mg/kg IV biweekly until disease recurrence or up to 1 year of dosing. This group comprised participants with Ewing's sarcoma refractory to prior treatment with at least 3 of the following agents: ifosfamide, etoposide, cyclophosphamide, doxorubicin, or vincristine.	Total n=219 Participants Total of all reporting groups
Age, Continuous	23.7 Years STANDARD_DEVIATION 15.5 • n=5 Participants	20.1 Years STANDARD_DEVIATION 10.3 • n=7 Participants	27.5 Years STANDARD_DEVIATION 15.3 • n=5 Participants	24.6 Years STANDARD_DEVIATION 11.4 • n=4 Participants	24.3 Years STANDARD_DEVIATION 12.8 • n=21 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	13 Participants n=7 Participants	11 Participants n=5 Participants	43 Participants n=4 Participants	81 Participants n=21 Participants
Sex: Female, Male Male	21 Participants n=5 Participants	20 Participants n=7 Participants	24 Participants n=5 Participants	73 Participants n=4 Participants	138 Participants n=21 Participants

PRIMARY outcome

Timeframe: Up to 1 year following the start of study therapy

Population: Participants in Group 3 with evaluable data.

Outcome measures

Outcome measures
Measure	Group 3: 10 mg/kg n=84 Participants Participants received robatumumab 10 mg/kg IV biweekly until disease recurrence or up to 1 year of dosing. This group comprised participants with Ewing's sarcoma refractory to prior treatment with at least 3 of the following agents: ifosfamide, etoposide, cyclophosphamide, doxorubicin, or vincristine.	Group 1: 10 mg/kg Participants received robatumumab 10 mg/kg IV as a single dose on Day 1, followed by surgery on Day 10 to 14, and four weeks later, resumption of robatumumab 10 mg/kg on the same calendar day (± 3 days) once every 2 weeks until disease recurrence or up to 1 year of dosing. This group comprised participants with resectable osteosarcoma that relapsed within 6 months of prior definitive treatment (eg surgical metastasectomy) and having at least one prior chemotherapy regimen containing a platinum agent and doxorubicin.	Group 2: 10 mg/kg Participants received robatumumab 10 mg/kg IV biweekly until disease recurrence or up to 1 year of dosing. This group comprised participants with relapsed and unresectable osteosarcoma refractory to prior chemotherapy with a platinum- and doxorubicin-containing regimen.	Group 3: 10 mg/kg Participants received robatumumab 10 mg/kg IV biweekly until disease recurrence or up to 1 year of dosing. This group comprised participants with Ewing's sarcoma refractory to prior treatment with at least 3 of the following agents: ifosfamide, etoposide, cyclophosphamide, doxorubicin, or vincristine.
Number of Participants Achieving a Complete Response or Partial Response (Group 3 Only)	6 Participants	—	—	—

PRIMARY outcome

Timeframe: Approximately 14 days

Population: Group 1 Participants; this outcome was not evaluated due to early termination of the study.

Tumor proliferation was measured using Ki-67 levels. Ki-67 is nuclear protein associated with cellular proliferation.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Up to 1 year following the start of study therapy

Population: Group 2 participants with evaluable data.

Responses to treatment (complete response, partial response, or stable disease) confirmed by central review for Participants in Group 2. Response was based on Response Evaluation Criteria in Solid Tumors (RECIST) and World Health Organization (WHO) criteria.

Outcome measures

Outcome measures
Measure	Group 3: 10 mg/kg n=29 Participants Participants received robatumumab 10 mg/kg IV biweekly until disease recurrence or up to 1 year of dosing. This group comprised participants with Ewing's sarcoma refractory to prior treatment with at least 3 of the following agents: ifosfamide, etoposide, cyclophosphamide, doxorubicin, or vincristine.	Group 1: 10 mg/kg Participants received robatumumab 10 mg/kg IV as a single dose on Day 1, followed by surgery on Day 10 to 14, and four weeks later, resumption of robatumumab 10 mg/kg on the same calendar day (± 3 days) once every 2 weeks until disease recurrence or up to 1 year of dosing. This group comprised participants with resectable osteosarcoma that relapsed within 6 months of prior definitive treatment (eg surgical metastasectomy) and having at least one prior chemotherapy regimen containing a platinum agent and doxorubicin.	Group 2: 10 mg/kg Participants received robatumumab 10 mg/kg IV biweekly until disease recurrence or up to 1 year of dosing. This group comprised participants with relapsed and unresectable osteosarcoma refractory to prior chemotherapy with a platinum- and doxorubicin-containing regimen.	Group 3: 10 mg/kg Participants received robatumumab 10 mg/kg IV biweekly until disease recurrence or up to 1 year of dosing. This group comprised participants with Ewing's sarcoma refractory to prior treatment with at least 3 of the following agents: ifosfamide, etoposide, cyclophosphamide, doxorubicin, or vincristine.
Number of Participants Achieving a Complete Response, a Partial Response, or Stable Disease (Group 2 Only)	6 Participants	—	—	—

SECONDARY outcome

Timeframe: From start of treatment until death or data analysis cut off (Up to 3.4 years)

Population: All study participants

This is a measure of the number of participants known to be alive at the time of data analysis for this study.

Outcome measures

Outcome measures
Measure	Group 3: 10 mg/kg n=35 Participants Participants received robatumumab 10 mg/kg IV biweekly until disease recurrence or up to 1 year of dosing. This group comprised participants with Ewing's sarcoma refractory to prior treatment with at least 3 of the following agents: ifosfamide, etoposide, cyclophosphamide, doxorubicin, or vincristine.	Group 1: 10 mg/kg n=33 Participants Participants received robatumumab 10 mg/kg IV as a single dose on Day 1, followed by surgery on Day 10 to 14, and four weeks later, resumption of robatumumab 10 mg/kg on the same calendar day (± 3 days) once every 2 weeks until disease recurrence or up to 1 year of dosing. This group comprised participants with resectable osteosarcoma that relapsed within 6 months of prior definitive treatment (eg surgical metastasectomy) and having at least one prior chemotherapy regimen containing a platinum agent and doxorubicin.	Group 2: 10 mg/kg n=35 Participants Participants received robatumumab 10 mg/kg IV biweekly until disease recurrence or up to 1 year of dosing. This group comprised participants with relapsed and unresectable osteosarcoma refractory to prior chemotherapy with a platinum- and doxorubicin-containing regimen.	Group 3: 10 mg/kg n=116 Participants Participants received robatumumab 10 mg/kg IV biweekly until disease recurrence or up to 1 year of dosing. This group comprised participants with Ewing's sarcoma refractory to prior treatment with at least 3 of the following agents: ifosfamide, etoposide, cyclophosphamide, doxorubicin, or vincristine.
Overall Survival	17 Participants	16 Participants	7 Participants	28 Participants

SECONDARY outcome

Timeframe: From start of treatment until relapse or data analysis cut off (Up to 3.4 years)

Population: Group 1 participants; this outcome was not evaluated due to early termination of the study.

This is a measure of the time from the start of the study to documented relapse of disease.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: End of infusion on Day 1, and then prior to surgery, before and after the 2nd, 3rd, and 8th doses (up to 20 weeks)

Population: Group 1, both dose levels: this outcome was not evaluated due to early termination of the study.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 2 years

Population: This outcome was not evaluated due to early termination of the study.

For biological agents, it is possible for the host (participant) to develop antibodies to the agent. This outcome measure was planned to find out the number of participants who developed the antibodies after treatment with robatumumab.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 2 years

Population: All participants receiving study drug.

An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment. Treatment-emergent adverse events are those that occur after participants have received study treatment, or existing adverse events that occurred during screening that increase in severity after study treatment. Adverse events in the Group 1: 0.3 mg/kg arm that occurred after switching to the 10 mg/kg dose are displayed under the originally assigned treatment.

Outcome measures

Outcome measures
Measure	Group 3: 10 mg/kg n=34 Participants Participants received robatumumab 10 mg/kg IV biweekly until disease recurrence or up to 1 year of dosing. This group comprised participants with Ewing's sarcoma refractory to prior treatment with at least 3 of the following agents: ifosfamide, etoposide, cyclophosphamide, doxorubicin, or vincristine.	Group 1: 10 mg/kg n=33 Participants Participants received robatumumab 10 mg/kg IV as a single dose on Day 1, followed by surgery on Day 10 to 14, and four weeks later, resumption of robatumumab 10 mg/kg on the same calendar day (± 3 days) once every 2 weeks until disease recurrence or up to 1 year of dosing. This group comprised participants with resectable osteosarcoma that relapsed within 6 months of prior definitive treatment (eg surgical metastasectomy) and having at least one prior chemotherapy regimen containing a platinum agent and doxorubicin.	Group 2: 10 mg/kg n=34 Participants Participants received robatumumab 10 mg/kg IV biweekly until disease recurrence or up to 1 year of dosing. This group comprised participants with relapsed and unresectable osteosarcoma refractory to prior chemotherapy with a platinum- and doxorubicin-containing regimen.	Group 3: 10 mg/kg n=115 Participants Participants received robatumumab 10 mg/kg IV biweekly until disease recurrence or up to 1 year of dosing. This group comprised participants with Ewing's sarcoma refractory to prior treatment with at least 3 of the following agents: ifosfamide, etoposide, cyclophosphamide, doxorubicin, or vincristine.
Number of Participants Experiencing Treatment-Emergent Adverse Events	31 Participants	30 Participants	31 Participants	112 Participants

SECONDARY outcome

Timeframe: From the start of treatment until disease progression or data analysis cut off (Up to 3.4 years)

Population: All participants in Groups 2 and 3; this outcome was not evaluated due to early termination of the study

This is a measure of the time from the start of the study to the time of documented disease progression.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From start of treatment until death or data analysis cut off (Up to 3.4 years)

Population: Group 2 and 3 Participants

This is a measure of the time of survival from first dose to documentation of death

Outcome measures

Outcome measures
Measure	Group 3: 10 mg/kg n=35 Participants Participants received robatumumab 10 mg/kg IV biweekly until disease recurrence or up to 1 year of dosing. This group comprised participants with Ewing's sarcoma refractory to prior treatment with at least 3 of the following agents: ifosfamide, etoposide, cyclophosphamide, doxorubicin, or vincristine.	Group 1: 10 mg/kg n=116 Participants Participants received robatumumab 10 mg/kg IV as a single dose on Day 1, followed by surgery on Day 10 to 14, and four weeks later, resumption of robatumumab 10 mg/kg on the same calendar day (± 3 days) once every 2 weeks until disease recurrence or up to 1 year of dosing. This group comprised participants with resectable osteosarcoma that relapsed within 6 months of prior definitive treatment (eg surgical metastasectomy) and having at least one prior chemotherapy regimen containing a platinum agent and doxorubicin.	Group 2: 10 mg/kg Participants received robatumumab 10 mg/kg IV biweekly until disease recurrence or up to 1 year of dosing. This group comprised participants with relapsed and unresectable osteosarcoma refractory to prior chemotherapy with a platinum- and doxorubicin-containing regimen.	Group 3: 10 mg/kg Participants received robatumumab 10 mg/kg IV biweekly until disease recurrence or up to 1 year of dosing. This group comprised participants with Ewing's sarcoma refractory to prior treatment with at least 3 of the following agents: ifosfamide, etoposide, cyclophosphamide, doxorubicin, or vincristine.
Overall Survival (Groups 2 and 3 Only)	8.18 Months Interval 2.96 to 10.58	6.93 Months Interval 4.93 to 11.1	—	—

SECONDARY outcome

Timeframe: From time of documented response until disease progression or data analysis cut off (Up to 3.4 years)

Population: Group 2 and 3 participants; this outcome was not evaluated due to early termination of the study

This is a measure of the amount of time in which the tumor responded to therapy.

Outcome measures

Outcome data not reported

Adverse Events

Group 1: 0.3mg/kg

Serious events: 17 serious events

Other events: 28 other events

Deaths: 0 deaths

Group 1: 10mg/kg

Serious events: 8 serious events

Other events: 30 other events

Deaths: 0 deaths

Group 2: 10mg/kg

Serious events: 12 serious events

Other events: 29 other events

Deaths: 0 deaths

Group 3: 10mg/kg

Serious events: 57 serious events

Other events: 104 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Investigator agrees not to publish or publicly present any interim results of the study without the prior written consent of the Sponsor. The Investigator further agrees to provide to the Sponsor 45 days prior to submission any publication, presentation, abstracts, manuscripts, or electronic media that report any results of the study. The Sponsor shall have the right to review and comment.
Publication restrictions are in place

Restriction type: OTHER