Trial Outcomes & Findings for A Eurosarc Study of Mifamurtide in Advanced Osteosarcoma (MEMOS) (NCT NCT02441309)

Last Updated: 2019-09-13

Results Overview

Biological response data based on pharmacodynamic endpoints on tumour biopsy material including macrophage infiltration and innate immune activation.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

8 participants

Primary outcome timeframe

Change from Baseline to after 6 weeks of treatment

Results posted on

2019-09-13

Participant Flow

Participant milestones

Participant milestones
Measure	A. Mifamurtide Only Patients receive Mifamurtide only. Treatment Weeks 1-6 (post 1st biopsy/resection): Mifamurtide 2mg/m2, IV infusion, twice/week, with each infusion given at least 3 days apart, for 6 weeks. Treatment Weeks 7-12 (post 2nd biopsy/resection): Mifamurtide 2mg/m2, IV infusion, twice/week, with each infusion given at least 3 days apart, for 6 weeks. Treatment Weeks 13-36: Mifamurtide 2mg/m2, IV infusion, once/week. Mifamurtide	B. Ifosfamide (Followed by Mifamurtide) Patients receive Ifosfamide alone initially, followed by ifosfamide plus mifamurtide, then mifamurtide alone. Treatment Weeks 1-6: Day 1 of 21: Ifosfamide 12-15g/m2 IV infused over 4-5 days as per local practice. Repeated every 21 days for 2 cycles (3 weeks=1 cycle). Treatment Weeks 7-12 (post 2nd biopsy/resection): Day 1 of 21: Ifosfamide 12-15g/m2 IV infused over 4-5 days once every 21 days for two cycles (3 weeks=1 cycle). Ifosfamide administered as per local practice, including concurrent dosing with mesna. Plus mifamurtide 2mg/m2, IV infusion, twice/week. Ifosfamide infusion must be started 24 hours prior to mifamurtide. Mifamurtide should be given on day 2 and either day 5 or day 6. Treatment Weeks 13-18: Mifamurtide 2mg/m2, IV infusion, twice/week. Treatment Weeks 19-42: Mifamurtide 2mg/m2, IV infusion, once/week. Mifamurtide Ifosfamide	C. Ifosfamide + Mifamurtide Patients receive mifamurtide combined with ifosfamide initially. Treatment Weeks 1-6: Day 1 of 21: Ifosfamide 12-15g/m2 IV infusion infused over 4-5 days once every 21 days for two cycles (3 weeks=1 cycle). Plus Mifamurtide 2 mg/m2, IV infusion, twice per week, with each infusion given at least 3 days apart, for 6 weeks. Ifosfamide infusion must be started 24 hours prior to mifamurtide. Mifamurtide should be given on day 2 and either day 5 or day 6. Treatment Weeks 7-12 (post 2nd biopsy/resection): Day 1 of 21: Ifosfamide 12-15g/m2 IV infusion infused over 4-5 days once every 21 days for two cycles (3 weeks = 1 cycle). Plus Mifamurtide 2mg/m2, IV infusion, twice per week, with each infusion given at least 3 days apart, for 6 weeks. Ifosfamide infusion must be started 24 hours prior to mifamurtide. Mifamurtide should be given on day 2 and either day 5 or day 6. Treatment Weeks 13-36: Mifamurtide 2mg/m2, IV infusion, once/week. Mifamurtide Ifosfamide
Overall Study STARTED	3	2	3
Overall Study Received Allocated Intervention	1	2	3
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	3	2	3

Reasons for withdrawal

Reasons for withdrawal
Measure	A. Mifamurtide Only Patients receive Mifamurtide only. Treatment Weeks 1-6 (post 1st biopsy/resection): Mifamurtide 2mg/m2, IV infusion, twice/week, with each infusion given at least 3 days apart, for 6 weeks. Treatment Weeks 7-12 (post 2nd biopsy/resection): Mifamurtide 2mg/m2, IV infusion, twice/week, with each infusion given at least 3 days apart, for 6 weeks. Treatment Weeks 13-36: Mifamurtide 2mg/m2, IV infusion, once/week. Mifamurtide	B. Ifosfamide (Followed by Mifamurtide) Patients receive Ifosfamide alone initially, followed by ifosfamide plus mifamurtide, then mifamurtide alone. Treatment Weeks 1-6: Day 1 of 21: Ifosfamide 12-15g/m2 IV infused over 4-5 days as per local practice. Repeated every 21 days for 2 cycles (3 weeks=1 cycle). Treatment Weeks 7-12 (post 2nd biopsy/resection): Day 1 of 21: Ifosfamide 12-15g/m2 IV infused over 4-5 days once every 21 days for two cycles (3 weeks=1 cycle). Ifosfamide administered as per local practice, including concurrent dosing with mesna. Plus mifamurtide 2mg/m2, IV infusion, twice/week. Ifosfamide infusion must be started 24 hours prior to mifamurtide. Mifamurtide should be given on day 2 and either day 5 or day 6. Treatment Weeks 13-18: Mifamurtide 2mg/m2, IV infusion, twice/week. Treatment Weeks 19-42: Mifamurtide 2mg/m2, IV infusion, once/week. Mifamurtide Ifosfamide	C. Ifosfamide + Mifamurtide Patients receive mifamurtide combined with ifosfamide initially. Treatment Weeks 1-6: Day 1 of 21: Ifosfamide 12-15g/m2 IV infusion infused over 4-5 days once every 21 days for two cycles (3 weeks=1 cycle). Plus Mifamurtide 2 mg/m2, IV infusion, twice per week, with each infusion given at least 3 days apart, for 6 weeks. Ifosfamide infusion must be started 24 hours prior to mifamurtide. Mifamurtide should be given on day 2 and either day 5 or day 6. Treatment Weeks 7-12 (post 2nd biopsy/resection): Day 1 of 21: Ifosfamide 12-15g/m2 IV infusion infused over 4-5 days once every 21 days for two cycles (3 weeks = 1 cycle). Plus Mifamurtide 2mg/m2, IV infusion, twice per week, with each infusion given at least 3 days apart, for 6 weeks. Ifosfamide infusion must be started 24 hours prior to mifamurtide. Mifamurtide should be given on day 2 and either day 5 or day 6. Treatment Weeks 13-36: Mifamurtide 2mg/m2, IV infusion, once/week. Mifamurtide Ifosfamide
Overall Study Disease progression	2	1	2
Overall Study Adverse Event	0	1	0
Overall Study Withdrawal by Subject	1	0	1

Baseline Characteristics

A Eurosarc Study of Mifamurtide in Advanced Osteosarcoma (MEMOS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	A. Mifamurtide Only n=3 Participants Patients receive Mifamurtide only. Treatment Weeks 1-6 (post 1st biopsy/resection): Mifamurtide 2mg/m2, IV infusion, twice/week, with each infusion given at least 3 days apart, for 6 weeks. Treatment Weeks 7-12 (post 2nd biopsy/resection): Mifamurtide 2mg/m2, IV infusion, twice/week, with each infusion given at least 3 days apart, for 6 weeks. Treatment Weeks 13-36: Mifamurtide 2mg/m2, IV infusion, once/week. Mifamurtide	B. Ifosfamide (Followed by Mifamurtide) n=2 Participants Patients receive Ifosfamide alone initially, followed by ifosfamide plus mifamurtide, then mifamurtide alone. Treatment Weeks 1-6: Day 1 of 21: Ifosfamide 12-15g/m2 IV infused over 4-5 days as per local practice. Repeated every 21 days for 2 cycles (3 weeks=1 cycle). Treatment Weeks 7-12 (post 2nd biopsy/resection): Day 1 of 21: Ifosfamide 12-15g/m2 IV infused over 4-5 days once every 21 days for two cycles (3 weeks=1 cycle). Ifosfamide administered as per local practice, including concurrent dosing with mesna. Plus mifamurtide 2mg/m2, IV infusion, twice/week. Ifosfamide infusion must be started 24 hours prior to mifamurtide. Mifamurtide should be given on day 2 and either day 5 or day 6. Treatment Weeks 13-18: Mifamurtide 2mg/m2, IV infusion, twice/week. Treatment Weeks 19-42: Mifamurtide 2mg/m2, IV infusion, once/week. Mifamurtide Ifosfamide	C. Ifosfamide + Mifamurtide n=3 Participants Patients receive mifamurtide combined with ifosfamide initially. Treatment Weeks 1-6: Day 1 of 21: Ifosfamide 12-15g/m2 IV infusion infused over 4-5 days once every 21 days for two cycles (3 weeks=1 cycle). Plus Mifamurtide 2 mg/m2, IV infusion, twice per week, with each infusion given at least 3 days apart, for 6 weeks. Ifosfamide infusion must be started 24 hours prior to mifamurtide. Mifamurtide should be given on day 2 and either day 5 or day 6. Treatment Weeks 7-12 (post 2nd biopsy/resection): Day 1 of 21: Ifosfamide 12-15g/m2 IV infusion infused over 4-5 days once every 21 days for two cycles (3 weeks = 1 cycle). Plus Mifamurtide 2mg/m2, IV infusion, twice per week, with each infusion given at least 3 days apart, for 6 weeks. Ifosfamide infusion must be started 24 hours prior to mifamurtide. Mifamurtide should be given on day 2 and either day 5 or day 6. Treatment Weeks 13-36: Mifamurtide 2mg/m2, IV infusion, once/week. Mifamurtide Ifosfamide	Total n=8 Participants Total of all reporting groups
Age, Continuous	21 years n=5 Participants	23 years n=7 Participants	57 years n=5 Participants	25 years n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants
Region of Enrollment Netherlands	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Region of Enrollment Norway	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Region of Enrollment United Kingdom	1 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Region of Enrollment Italy	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
WHO Performance Status 0	3 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
WHO Performance Status 1	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Histology/Cytological type Chondroblastic OS - 9181/3	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Histology/Cytological type Osteoblastic OS - 9180/3	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Histology/Cytological type Osteosarcoma NOS - 9180/3	1 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Primary Site Axial	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Primary Site Limb	2 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Disease stage at screening - Metastatic	3 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	8 Participants n=4 Participants
Tumour size at baseline (sum of longest diameters) (mm)	84 mm n=5 Participants	37 mm n=7 Participants	99 mm n=5 Participants	82 mm n=4 Participants
Prior chemotherapy Yes	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Prior chemotherapy No	2 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Prior radiotherapy Yes	3 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	8 Participants n=4 Participants
Prior radiotherapy No	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Prior surgery Yes	3 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	8 Participants n=4 Participants
Prior surgery No	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: Change from Baseline to after 6 weeks of treatment

Population: Insufficient number of participants for events for both primary and secondary objectives. The study stopped prematurely because of poor recruitment, meaning that no complete statistical analysis was possible as there were insufficient events and data were not collected.

Biological response data based on pharmacodynamic endpoints on tumour biopsy material including macrophage infiltration and innate immune activation.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Change from Baseline to after 6 weeks of treatment

Population: All patients are included since this is an intention to treat analysis.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) assessed by CT or MRI: Complete Response (CR): Disappearance of all target and non-target lesions Partial Response (PR): \>=30% decrease in the sum of the longest diameter of target lesions, AND no evidence of progression in non-target lesions, AND no new lesions Stable Disease (SD): sum of longest diameter of target lesions between PR and PD values, AND no evidence of progression in non-target lesions, AND no new lesions Progressive Disease (PD): \>20% increase in the sum of the longest diameter of target lesions, OR evidence of progression in non-target lesions, OR evidence of new lesions

Outcome measures

Outcome measures
Measure	A. Mifamurtide Only n=3 Participants Patients receive Mifamurtide only. Treatment Weeks 1-6 (post 1st biopsy/resection): Mifamurtide 2mg/m2, IV infusion, twice/week, with each infusion given at least 3 days apart, for 6 weeks. Treatment Weeks 7-12 (post 2nd biopsy/resection): Mifamurtide 2mg/m2, IV infusion, twice/week, with each infusion given at least 3 days apart, for 6 weeks. Treatment Weeks 13-36: Mifamurtide 2mg/m2, IV infusion, once/week. Mifamurtide	B. Ifosfamide (Followed by Mifamurtide) n=2 Participants Patients receive Ifosfamide alone initially, followed by ifosfamide plus mifamurtide, then mifamurtide alone. Treatment Weeks 1-6: Day 1 of 21: Ifosfamide 12-15g/m2 IV infused over 4-5 days as per local practice. Repeated every 21 days for 2 cycles (3 weeks=1 cycle). Treatment Weeks 7-12 (post 2nd biopsy/resection): Day 1 of 21: Ifosfamide 12-15g/m2 IV infused over 4-5 days once every 21 days for two cycles (3 weeks=1 cycle). Ifosfamide administered as per local practice, including concurrent dosing with mesna. Plus mifamurtide 2mg/m2, IV infusion, twice/week. Ifosfamide infusion must be started 24 hours prior to mifamurtide. Mifamurtide should be given on day 2 and either day 5 or day 6. Treatment Weeks 13-18: Mifamurtide 2mg/m2, IV infusion, twice/week. Treatment Weeks 19-42: Mifamurtide 2mg/m2, IV infusion, once/week. Mifamurtide Ifosfamide	C. Ifosfamide + Mifamurtide n=3 Participants Patients receive mifamurtide combined with ifosfamide initially. Treatment Weeks 1-6: Day 1 of 21: Ifosfamide 12-15g/m2 IV infusion infused over 4-5 days once every 21 days for two cycles (3 weeks=1 cycle). Plus Mifamurtide 2 mg/m2, IV infusion, twice per week, with each infusion given at least 3 days apart, for 6 weeks. Ifosfamide infusion must be started 24 hours prior to mifamurtide. Mifamurtide should be given on day 2 and either day 5 or day 6. Treatment Weeks 7-12 (post 2nd biopsy/resection): Day 1 of 21: Ifosfamide 12-15g/m2 IV infusion infused over 4-5 days once every 21 days for two cycles (3 weeks = 1 cycle). Plus Mifamurtide 2mg/m2, IV infusion, twice per week, with each infusion given at least 3 days apart, for 6 weeks. Ifosfamide infusion must be started 24 hours prior to mifamurtide. Mifamurtide should be given on day 2 and either day 5 or day 6. Treatment Weeks 13-36: Mifamurtide 2mg/m2, IV infusion, once/week. Mifamurtide Ifosfamide
Radiological Response Defined as Complete or Partial Response and Assessed Using RECIST Criteria Stable Disease (SD)	0 Participants	1 Participants	1 Participants
Radiological Response Defined as Complete or Partial Response and Assessed Using RECIST Criteria Progressive Disease (PD)	0 Participants	0 Participants	1 Participants
Radiological Response Defined as Complete or Partial Response and Assessed Using RECIST Criteria Patient did not reach endpoint	1 Participants	1 Participants	1 Participants
Radiological Response Defined as Complete or Partial Response and Assessed Using RECIST Criteria Patient progressed prior to time point	2 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Change from Baseline to after 12, 18, 24 & 36 weeks and end of treatment visit

Population: The end of treatment visit was completed by patients who were deemed to progress or withdrew from trial treatment at a time that a scheduled scan was not due to be taken. This end of treatment visit was used to confirm radiological progression.

Outcome measures

Outcome measures
Measure	A. Mifamurtide Only n=3 Participants Patients receive Mifamurtide only. Treatment Weeks 1-6 (post 1st biopsy/resection): Mifamurtide 2mg/m2, IV infusion, twice/week, with each infusion given at least 3 days apart, for 6 weeks. Treatment Weeks 7-12 (post 2nd biopsy/resection): Mifamurtide 2mg/m2, IV infusion, twice/week, with each infusion given at least 3 days apart, for 6 weeks. Treatment Weeks 13-36: Mifamurtide 2mg/m2, IV infusion, once/week. Mifamurtide	B. Ifosfamide (Followed by Mifamurtide) n=2 Participants Patients receive Ifosfamide alone initially, followed by ifosfamide plus mifamurtide, then mifamurtide alone. Treatment Weeks 1-6: Day 1 of 21: Ifosfamide 12-15g/m2 IV infused over 4-5 days as per local practice. Repeated every 21 days for 2 cycles (3 weeks=1 cycle). Treatment Weeks 7-12 (post 2nd biopsy/resection): Day 1 of 21: Ifosfamide 12-15g/m2 IV infused over 4-5 days once every 21 days for two cycles (3 weeks=1 cycle). Ifosfamide administered as per local practice, including concurrent dosing with mesna. Plus mifamurtide 2mg/m2, IV infusion, twice/week. Ifosfamide infusion must be started 24 hours prior to mifamurtide. Mifamurtide should be given on day 2 and either day 5 or day 6. Treatment Weeks 13-18: Mifamurtide 2mg/m2, IV infusion, twice/week. Treatment Weeks 19-42: Mifamurtide 2mg/m2, IV infusion, once/week. Mifamurtide Ifosfamide	C. Ifosfamide + Mifamurtide n=3 Participants Patients receive mifamurtide combined with ifosfamide initially. Treatment Weeks 1-6: Day 1 of 21: Ifosfamide 12-15g/m2 IV infusion infused over 4-5 days once every 21 days for two cycles (3 weeks=1 cycle). Plus Mifamurtide 2 mg/m2, IV infusion, twice per week, with each infusion given at least 3 days apart, for 6 weeks. Ifosfamide infusion must be started 24 hours prior to mifamurtide. Mifamurtide should be given on day 2 and either day 5 or day 6. Treatment Weeks 7-12 (post 2nd biopsy/resection): Day 1 of 21: Ifosfamide 12-15g/m2 IV infusion infused over 4-5 days once every 21 days for two cycles (3 weeks = 1 cycle). Plus Mifamurtide 2mg/m2, IV infusion, twice per week, with each infusion given at least 3 days apart, for 6 weeks. Ifosfamide infusion must be started 24 hours prior to mifamurtide. Mifamurtide should be given on day 2 and either day 5 or day 6. Treatment Weeks 13-36: Mifamurtide 2mg/m2, IV infusion, once/week. Mifamurtide Ifosfamide
Objective Radiological Response Based on RECIST v1.1 Week 12 · Stable Disease (SD)	0 Participants	1 Participants	1 Participants
Objective Radiological Response Based on RECIST v1.1 Week 12 · Progressive Disease (PD)	0 Participants	0 Participants	0 Participants
Objective Radiological Response Based on RECIST v1.1 Week 12 · Patient did not reach endpoint	3 Participants	1 Participants	2 Participants
Objective Radiological Response Based on RECIST v1.1 Week 18 · Stable Disease (SD)	0 Participants	1 Participants	0 Participants
Objective Radiological Response Based on RECIST v1.1 Week 18 · Progressive Disease (PD)	0 Participants	0 Participants	1 Participants
Objective Radiological Response Based on RECIST v1.1 Week 18 · Patient did not reach endpoint	3 Participants	1 Participants	2 Participants
Objective Radiological Response Based on RECIST v1.1 Week 24 · Stable Disease (SD)	0 Participants	1 Participants	0 Participants
Objective Radiological Response Based on RECIST v1.1 Week 24 · Progressive Disease (PD)	0 Participants	0 Participants	0 Participants
Objective Radiological Response Based on RECIST v1.1 Week 24 · Patient did not reach endpoint	3 Participants	1 Participants	3 Participants
Objective Radiological Response Based on RECIST v1.1 Week 36 · Stable Disease (SD)	0 Participants	0 Participants	0 Participants
Objective Radiological Response Based on RECIST v1.1 Week 36 · Progressive Disease (PD)	0 Participants	1 Participants	0 Participants
Objective Radiological Response Based on RECIST v1.1 Week 36 · Patient did not reach endpoint	3 Participants	1 Participants	3 Participants
Objective Radiological Response Based on RECIST v1.1 End of Treatment visit (prior to week 6) · Stable Disease (SD)	0 Participants	0 Participants	0 Participants
Objective Radiological Response Based on RECIST v1.1 End of Treatment visit (prior to week 6) · Progressive Disease (PD)	2 Participants	0 Participants	0 Participants
Objective Radiological Response Based on RECIST v1.1 End of Treatment visit (prior to week 6) · Patient did not reach endpoint	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 42 weeks

Population: Intention to treat

Toxicity measured and graded according to Common Terminology Criteria for Adverse Events v4.0 (CTCAE) Grade refers to the severity of the adverse event. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3 Severe; medically significant but not immediately life-threatening; hospitalisation or prolongation of hospitalisation indicated; disabling or limiting self care activities of daily living. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.

Outcome measures

Outcome measures
Measure	A. Mifamurtide Only n=3 Participants Patients receive Mifamurtide only. Treatment Weeks 1-6 (post 1st biopsy/resection): Mifamurtide 2mg/m2, IV infusion, twice/week, with each infusion given at least 3 days apart, for 6 weeks. Treatment Weeks 7-12 (post 2nd biopsy/resection): Mifamurtide 2mg/m2, IV infusion, twice/week, with each infusion given at least 3 days apart, for 6 weeks. Treatment Weeks 13-36: Mifamurtide 2mg/m2, IV infusion, once/week. Mifamurtide	B. Ifosfamide (Followed by Mifamurtide) n=2 Participants Patients receive Ifosfamide alone initially, followed by ifosfamide plus mifamurtide, then mifamurtide alone. Treatment Weeks 1-6: Day 1 of 21: Ifosfamide 12-15g/m2 IV infused over 4-5 days as per local practice. Repeated every 21 days for 2 cycles (3 weeks=1 cycle). Treatment Weeks 7-12 (post 2nd biopsy/resection): Day 1 of 21: Ifosfamide 12-15g/m2 IV infused over 4-5 days once every 21 days for two cycles (3 weeks=1 cycle). Ifosfamide administered as per local practice, including concurrent dosing with mesna. Plus mifamurtide 2mg/m2, IV infusion, twice/week. Ifosfamide infusion must be started 24 hours prior to mifamurtide. Mifamurtide should be given on day 2 and either day 5 or day 6. Treatment Weeks 13-18: Mifamurtide 2mg/m2, IV infusion, twice/week. Treatment Weeks 19-42: Mifamurtide 2mg/m2, IV infusion, once/week. Mifamurtide Ifosfamide	C. Ifosfamide + Mifamurtide n=3 Participants Patients receive mifamurtide combined with ifosfamide initially. Treatment Weeks 1-6: Day 1 of 21: Ifosfamide 12-15g/m2 IV infusion infused over 4-5 days once every 21 days for two cycles (3 weeks=1 cycle). Plus Mifamurtide 2 mg/m2, IV infusion, twice per week, with each infusion given at least 3 days apart, for 6 weeks. Ifosfamide infusion must be started 24 hours prior to mifamurtide. Mifamurtide should be given on day 2 and either day 5 or day 6. Treatment Weeks 7-12 (post 2nd biopsy/resection): Day 1 of 21: Ifosfamide 12-15g/m2 IV infusion infused over 4-5 days once every 21 days for two cycles (3 weeks = 1 cycle). Plus Mifamurtide 2mg/m2, IV infusion, twice per week, with each infusion given at least 3 days apart, for 6 weeks. Ifosfamide infusion must be started 24 hours prior to mifamurtide. Mifamurtide should be given on day 2 and either day 5 or day 6. Treatment Weeks 13-36: Mifamurtide 2mg/m2, IV infusion, once/week. Mifamurtide Ifosfamide
Number of Patients Experiencing a Grade 3 or More Severe Adverse Event (Graded According to CTCAE Criteria v4.0)	1 Participants	2 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to 42 weeks

Population: Intention to treat

A laboratory abnormality is defined as an adverse event of grade 3 or 4 identified by a laboratory test of participant blood samples. Adverse events were graded according to Common Terminology Criteria for Adverse Events v4.0 (CTCAE).

Outcome measures

Outcome measures
Measure	A. Mifamurtide Only n=3 Participants Patients receive Mifamurtide only. Treatment Weeks 1-6 (post 1st biopsy/resection): Mifamurtide 2mg/m2, IV infusion, twice/week, with each infusion given at least 3 days apart, for 6 weeks. Treatment Weeks 7-12 (post 2nd biopsy/resection): Mifamurtide 2mg/m2, IV infusion, twice/week, with each infusion given at least 3 days apart, for 6 weeks. Treatment Weeks 13-36: Mifamurtide 2mg/m2, IV infusion, once/week. Mifamurtide	B. Ifosfamide (Followed by Mifamurtide) n=2 Participants Patients receive Ifosfamide alone initially, followed by ifosfamide plus mifamurtide, then mifamurtide alone. Treatment Weeks 1-6: Day 1 of 21: Ifosfamide 12-15g/m2 IV infused over 4-5 days as per local practice. Repeated every 21 days for 2 cycles (3 weeks=1 cycle). Treatment Weeks 7-12 (post 2nd biopsy/resection): Day 1 of 21: Ifosfamide 12-15g/m2 IV infused over 4-5 days once every 21 days for two cycles (3 weeks=1 cycle). Ifosfamide administered as per local practice, including concurrent dosing with mesna. Plus mifamurtide 2mg/m2, IV infusion, twice/week. Ifosfamide infusion must be started 24 hours prior to mifamurtide. Mifamurtide should be given on day 2 and either day 5 or day 6. Treatment Weeks 13-18: Mifamurtide 2mg/m2, IV infusion, twice/week. Treatment Weeks 19-42: Mifamurtide 2mg/m2, IV infusion, once/week. Mifamurtide Ifosfamide	C. Ifosfamide + Mifamurtide n=3 Participants Patients receive mifamurtide combined with ifosfamide initially. Treatment Weeks 1-6: Day 1 of 21: Ifosfamide 12-15g/m2 IV infusion infused over 4-5 days once every 21 days for two cycles (3 weeks=1 cycle). Plus Mifamurtide 2 mg/m2, IV infusion, twice per week, with each infusion given at least 3 days apart, for 6 weeks. Ifosfamide infusion must be started 24 hours prior to mifamurtide. Mifamurtide should be given on day 2 and either day 5 or day 6. Treatment Weeks 7-12 (post 2nd biopsy/resection): Day 1 of 21: Ifosfamide 12-15g/m2 IV infusion infused over 4-5 days once every 21 days for two cycles (3 weeks = 1 cycle). Plus Mifamurtide 2mg/m2, IV infusion, twice per week, with each infusion given at least 3 days apart, for 6 weeks. Ifosfamide infusion must be started 24 hours prior to mifamurtide. Mifamurtide should be given on day 2 and either day 5 or day 6. Treatment Weeks 13-36: Mifamurtide 2mg/m2, IV infusion, once/week. Mifamurtide Ifosfamide
Number of Patients Experiencing a Laboratory Abnormality (Grade 3-4)	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 42 weeks

Population: Intention to treat

Median time from death attributed to the disease. Censored at last known time alive or death from other causes.

Outcome measures

Outcome measures
Measure	A. Mifamurtide Only n=3 Participants Patients receive Mifamurtide only. Treatment Weeks 1-6 (post 1st biopsy/resection): Mifamurtide 2mg/m2, IV infusion, twice/week, with each infusion given at least 3 days apart, for 6 weeks. Treatment Weeks 7-12 (post 2nd biopsy/resection): Mifamurtide 2mg/m2, IV infusion, twice/week, with each infusion given at least 3 days apart, for 6 weeks. Treatment Weeks 13-36: Mifamurtide 2mg/m2, IV infusion, once/week. Mifamurtide	B. Ifosfamide (Followed by Mifamurtide) n=2 Participants Patients receive Ifosfamide alone initially, followed by ifosfamide plus mifamurtide, then mifamurtide alone. Treatment Weeks 1-6: Day 1 of 21: Ifosfamide 12-15g/m2 IV infused over 4-5 days as per local practice. Repeated every 21 days for 2 cycles (3 weeks=1 cycle). Treatment Weeks 7-12 (post 2nd biopsy/resection): Day 1 of 21: Ifosfamide 12-15g/m2 IV infused over 4-5 days once every 21 days for two cycles (3 weeks=1 cycle). Ifosfamide administered as per local practice, including concurrent dosing with mesna. Plus mifamurtide 2mg/m2, IV infusion, twice/week. Ifosfamide infusion must be started 24 hours prior to mifamurtide. Mifamurtide should be given on day 2 and either day 5 or day 6. Treatment Weeks 13-18: Mifamurtide 2mg/m2, IV infusion, twice/week. Treatment Weeks 19-42: Mifamurtide 2mg/m2, IV infusion, once/week. Mifamurtide Ifosfamide	C. Ifosfamide + Mifamurtide n=3 Participants Patients receive mifamurtide combined with ifosfamide initially. Treatment Weeks 1-6: Day 1 of 21: Ifosfamide 12-15g/m2 IV infusion infused over 4-5 days once every 21 days for two cycles (3 weeks=1 cycle). Plus Mifamurtide 2 mg/m2, IV infusion, twice per week, with each infusion given at least 3 days apart, for 6 weeks. Ifosfamide infusion must be started 24 hours prior to mifamurtide. Mifamurtide should be given on day 2 and either day 5 or day 6. Treatment Weeks 7-12 (post 2nd biopsy/resection): Day 1 of 21: Ifosfamide 12-15g/m2 IV infusion infused over 4-5 days once every 21 days for two cycles (3 weeks = 1 cycle). Plus Mifamurtide 2mg/m2, IV infusion, twice per week, with each infusion given at least 3 days apart, for 6 weeks. Ifosfamide infusion must be started 24 hours prior to mifamurtide. Mifamurtide should be given on day 2 and either day 5 or day 6. Treatment Weeks 13-36: Mifamurtide 2mg/m2, IV infusion, once/week. Mifamurtide Ifosfamide
Disease Specific Overall Survival	0.7 months Interval 0.2 to Undefined upper confidence interval (insufficient number of participants with events).	9.2 months Interval 9.2 to Undefined upper confidence interval (insufficient number of participants with events).	2.8 months Interval 1.5 to Undefined upper confidence interval (insufficient number of participants with events).

SECONDARY outcome

Timeframe: Up to 42 weeks

Population: Intention to treat

Time from randomisation for deemed non-resectable groups, or time from registration for deemed resectable group to first event, where an event is Progressive Disease as (defined by RECIST criterion v1.1) or death due to any cause. Patients who have not had an event will be censored at their last follow-up date. Patients lost to follow-up without an event will be censored at the date of their last consultation. Progressive disease according to RECIST v1.1 is defined as a \>=20% increase in the sum of long diameters of target lesions, OR progression of non-target lesions, OR evidence of new lesions.

Outcome measures

Outcome measures
Measure	A. Mifamurtide Only n=3 Participants Patients receive Mifamurtide only. Treatment Weeks 1-6 (post 1st biopsy/resection): Mifamurtide 2mg/m2, IV infusion, twice/week, with each infusion given at least 3 days apart, for 6 weeks. Treatment Weeks 7-12 (post 2nd biopsy/resection): Mifamurtide 2mg/m2, IV infusion, twice/week, with each infusion given at least 3 days apart, for 6 weeks. Treatment Weeks 13-36: Mifamurtide 2mg/m2, IV infusion, once/week. Mifamurtide	B. Ifosfamide (Followed by Mifamurtide) n=2 Participants Patients receive Ifosfamide alone initially, followed by ifosfamide plus mifamurtide, then mifamurtide alone. Treatment Weeks 1-6: Day 1 of 21: Ifosfamide 12-15g/m2 IV infused over 4-5 days as per local practice. Repeated every 21 days for 2 cycles (3 weeks=1 cycle). Treatment Weeks 7-12 (post 2nd biopsy/resection): Day 1 of 21: Ifosfamide 12-15g/m2 IV infused over 4-5 days once every 21 days for two cycles (3 weeks=1 cycle). Ifosfamide administered as per local practice, including concurrent dosing with mesna. Plus mifamurtide 2mg/m2, IV infusion, twice/week. Ifosfamide infusion must be started 24 hours prior to mifamurtide. Mifamurtide should be given on day 2 and either day 5 or day 6. Treatment Weeks 13-18: Mifamurtide 2mg/m2, IV infusion, twice/week. Treatment Weeks 19-42: Mifamurtide 2mg/m2, IV infusion, once/week. Mifamurtide Ifosfamide	C. Ifosfamide + Mifamurtide n=3 Participants Patients receive mifamurtide combined with ifosfamide initially. Treatment Weeks 1-6: Day 1 of 21: Ifosfamide 12-15g/m2 IV infusion infused over 4-5 days once every 21 days for two cycles (3 weeks=1 cycle). Plus Mifamurtide 2 mg/m2, IV infusion, twice per week, with each infusion given at least 3 days apart, for 6 weeks. Ifosfamide infusion must be started 24 hours prior to mifamurtide. Mifamurtide should be given on day 2 and either day 5 or day 6. Treatment Weeks 7-12 (post 2nd biopsy/resection): Day 1 of 21: Ifosfamide 12-15g/m2 IV infusion infused over 4-5 days once every 21 days for two cycles (3 weeks = 1 cycle). Plus Mifamurtide 2mg/m2, IV infusion, twice per week, with each infusion given at least 3 days apart, for 6 weeks. Ifosfamide infusion must be started 24 hours prior to mifamurtide. Mifamurtide should be given on day 2 and either day 5 or day 6. Treatment Weeks 13-36: Mifamurtide 2mg/m2, IV infusion, once/week. Mifamurtide Ifosfamide
Progression Free Survival	NA months No events were observed, median is undefined.	NA months No events were observed, median is undefined.	7.0 months Interval 4.6 to Undefined upper confidence interval (insufficient number of participants with events).

SECONDARY outcome

Timeframe: During screening, and weeks 1, 4, 6 and 7. Then every 3 weeks during treatment.

Biological response based on systemic levels of mifamurtide activated cytokines.

Outcome measures

Outcome data not reported

Adverse Events

A. Mifamurtide Only

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

B. Ifosfamide (Followed by Mifamurtide)

Serious events: 2 serious events

Other events: 2 other events

Deaths: 0 deaths

C. Ifosfamide + Mifamurtide

Serious events: 2 serious events

Other events: 3 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	A. Mifamurtide Only n=3 participants at risk Patients receive Mifamurtide only. Treatment Weeks 1-6 (post 1st biopsy/resection): Mifamurtide 2mg/m2, IV infusion, twice/week, with each infusion given at least 3 days apart, for 6 weeks. Treatment Weeks 7-12 (post 2nd biopsy/resection): Mifamurtide 2mg/m2, IV infusion, twice/week, with each infusion given at least 3 days apart, for 6 weeks. Treatment Weeks 13-36: Mifamurtide 2mg/m2, IV infusion, once/week. Mifamurtide	B. Ifosfamide (Followed by Mifamurtide) n=2 participants at risk Patients receive Ifosfamide alone initially, followed by ifosfamide plus mifamurtide, then mifamurtide alone. Treatment Weeks 1-6: Day 1 of 21: Ifosfamide 12-15g/m2 IV infused over 4-5 days as per local practice. Repeated every 21 days for 2 cycles (3 weeks=1 cycle). Treatment Weeks 7-12 (post 2nd biopsy/resection): Day 1 of 21: Ifosfamide 12-15g/m2 IV infused over 4-5 days once every 21 days for two cycles (3 weeks=1 cycle). Ifosfamide administered as per local practice, including concurrent dosing with mesna. Plus mifamurtide 2mg/m2, IV infusion, twice/week. Ifosfamide infusion must be started 24 hours prior to mifamurtide. Mifamurtide should be given on day 2 and either day 5 or day 6. Treatment Weeks 13-18: Mifamurtide 2mg/m2, IV infusion, twice/week. Treatment Weeks 19-42: Mifamurtide 2mg/m2, IV infusion, once/week. Mifamurtide Ifosfamide	C. Ifosfamide + Mifamurtide n=3 participants at risk Patients receive mifamurtide combined with ifosfamide initially. Treatment Weeks 1-6: Day 1 of 21: Ifosfamide 12-15g/m2 IV infusion infused over 4-5 days once every 21 days for two cycles (3 weeks=1 cycle). Plus Mifamurtide 2 mg/m2, IV infusion, twice per week, with each infusion given at least 3 days apart, for 6 weeks. Ifosfamide infusion must be started 24 hours prior to mifamurtide. Mifamurtide should be given on day 2 and either day 5 or day 6. Treatment Weeks 7-12 (post 2nd biopsy/resection): Day 1 of 21: Ifosfamide 12-15g/m2 IV infusion infused over 4-5 days once every 21 days for two cycles (3 weeks = 1 cycle). Plus Mifamurtide 2mg/m2, IV infusion, twice per week, with each infusion given at least 3 days apart, for 6 weeks. Ifosfamide infusion must be started 24 hours prior to mifamurtide. Mifamurtide should be given on day 2 and either day 5 or day 6. Treatment Weeks 13-36: Mifamurtide 2mg/m2, IV infusion, once/week. Mifamurtide Ifosfamide
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/3 • Adverse events were collected from registration until the end of treatment (42 weeks) or the withdrawal of treatment. An abnormal laboratory value will not be assessed as an AE unless that value leads to discontinuation or delay in treatment, dose modification, therapeutic intervention, or is considered by the investigator to be a clinically significant change from baseline.	0.00% 0/2 • Adverse events were collected from registration until the end of treatment (42 weeks) or the withdrawal of treatment. An abnormal laboratory value will not be assessed as an AE unless that value leads to discontinuation or delay in treatment, dose modification, therapeutic intervention, or is considered by the investigator to be a clinically significant change from baseline.	33.3% 1/3 • Adverse events were collected from registration until the end of treatment (42 weeks) or the withdrawal of treatment. An abnormal laboratory value will not be assessed as an AE unless that value leads to discontinuation or delay in treatment, dose modification, therapeutic intervention, or is considered by the investigator to be a clinically significant change from baseline.
Infections and infestations Pseudomonas infection	0.00% 0/3 • Adverse events were collected from registration until the end of treatment (42 weeks) or the withdrawal of treatment. An abnormal laboratory value will not be assessed as an AE unless that value leads to discontinuation or delay in treatment, dose modification, therapeutic intervention, or is considered by the investigator to be a clinically significant change from baseline.	0.00% 0/2 • Adverse events were collected from registration until the end of treatment (42 weeks) or the withdrawal of treatment. An abnormal laboratory value will not be assessed as an AE unless that value leads to discontinuation or delay in treatment, dose modification, therapeutic intervention, or is considered by the investigator to be a clinically significant change from baseline.	33.3% 1/3 • Adverse events were collected from registration until the end of treatment (42 weeks) or the withdrawal of treatment. An abnormal laboratory value will not be assessed as an AE unless that value leads to discontinuation or delay in treatment, dose modification, therapeutic intervention, or is considered by the investigator to be a clinically significant change from baseline.
Infections and infestations Urinary tract infection	0.00% 0/3 • Adverse events were collected from registration until the end of treatment (42 weeks) or the withdrawal of treatment. An abnormal laboratory value will not be assessed as an AE unless that value leads to discontinuation or delay in treatment, dose modification, therapeutic intervention, or is considered by the investigator to be a clinically significant change from baseline.	50.0% 1/2 • Adverse events were collected from registration until the end of treatment (42 weeks) or the withdrawal of treatment. An abnormal laboratory value will not be assessed as an AE unless that value leads to discontinuation or delay in treatment, dose modification, therapeutic intervention, or is considered by the investigator to be a clinically significant change from baseline.	0.00% 0/3 • Adverse events were collected from registration until the end of treatment (42 weeks) or the withdrawal of treatment. An abnormal laboratory value will not be assessed as an AE unless that value leads to discontinuation or delay in treatment, dose modification, therapeutic intervention, or is considered by the investigator to be a clinically significant change from baseline.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/3 • Adverse events were collected from registration until the end of treatment (42 weeks) or the withdrawal of treatment. An abnormal laboratory value will not be assessed as an AE unless that value leads to discontinuation or delay in treatment, dose modification, therapeutic intervention, or is considered by the investigator to be a clinically significant change from baseline.	50.0% 1/2 • Adverse events were collected from registration until the end of treatment (42 weeks) or the withdrawal of treatment. An abnormal laboratory value will not be assessed as an AE unless that value leads to discontinuation or delay in treatment, dose modification, therapeutic intervention, or is considered by the investigator to be a clinically significant change from baseline.	0.00% 0/3 • Adverse events were collected from registration until the end of treatment (42 weeks) or the withdrawal of treatment. An abnormal laboratory value will not be assessed as an AE unless that value leads to discontinuation or delay in treatment, dose modification, therapeutic intervention, or is considered by the investigator to be a clinically significant change from baseline.
Nervous system disorders Hypophosphataemia	0.00% 0/3 • Adverse events were collected from registration until the end of treatment (42 weeks) or the withdrawal of treatment. An abnormal laboratory value will not be assessed as an AE unless that value leads to discontinuation or delay in treatment, dose modification, therapeutic intervention, or is considered by the investigator to be a clinically significant change from baseline.	50.0% 1/2 • Adverse events were collected from registration until the end of treatment (42 weeks) or the withdrawal of treatment. An abnormal laboratory value will not be assessed as an AE unless that value leads to discontinuation or delay in treatment, dose modification, therapeutic intervention, or is considered by the investigator to be a clinically significant change from baseline.	0.00% 0/3 • Adverse events were collected from registration until the end of treatment (42 weeks) or the withdrawal of treatment. An abnormal laboratory value will not be assessed as an AE unless that value leads to discontinuation or delay in treatment, dose modification, therapeutic intervention, or is considered by the investigator to be a clinically significant change from baseline.
Nervous system disorders Encephalopathy	0.00% 0/3 • Adverse events were collected from registration until the end of treatment (42 weeks) or the withdrawal of treatment. An abnormal laboratory value will not be assessed as an AE unless that value leads to discontinuation or delay in treatment, dose modification, therapeutic intervention, or is considered by the investigator to be a clinically significant change from baseline.	0.00% 0/2 • Adverse events were collected from registration until the end of treatment (42 weeks) or the withdrawal of treatment. An abnormal laboratory value will not be assessed as an AE unless that value leads to discontinuation or delay in treatment, dose modification, therapeutic intervention, or is considered by the investigator to be a clinically significant change from baseline.	33.3% 1/3 • Adverse events were collected from registration until the end of treatment (42 weeks) or the withdrawal of treatment. An abnormal laboratory value will not be assessed as an AE unless that value leads to discontinuation or delay in treatment, dose modification, therapeutic intervention, or is considered by the investigator to be a clinically significant change from baseline.

Other adverse events

Additional Information

Joint Research Office

University of Oxford

Phone: +441865572245

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place