Trial Outcomes & Findings for A Study of Olaratumab (LY3012207), Doxorubicin, and Ifosfamide in Participants With Advanced or Metastatic Soft Tissue Sarcoma (NCT NCT03283696)

Last Updated: 2020-09-10

Results Overview

A Dose Limiting Toxicity is defined as an Adverse Event (AE) that is likely related to the study medication or combination, and fulfills any one of the following criteria, graded according to the NCI-CTCAE Version 4.0: 1. Grade 3 or 4 febrile neutropenia, or sepsis., or 2. Grade 4 neutropenia lasting 7 days or longer. 3. Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia complicated by hemorrhage. 4. Nonhematologic Grade ≥3 toxicity, except for toxicities (such as nausea, vomiting, transient electrolyte abnormalities, or diarrhoea) that can be controlled with optimal medical management within 48 hours or clinically non-significant laboratory abnormalities.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

24 participants

Primary outcome timeframe

Cycle 1 (Up To 24 days)

Results posted on

2020-09-10

Participant Flow

Completers included participants who died from any cause, participants with progressive disease.

Participant milestones

Participant milestones
Measure	Olaratumab 15 mg/kg + Doxorubicin + Ifosfamide Participants received olaratumab 15 milligrams per kilogram (mg/kg) on days 1, 8 plus doxorubicin 25 milligrams per meter square (mg/m\^2) on days 1, 2, 3 plus ifosfamide 2.5 gram per meter square (g/m\^2) per day on days 1, 2, 3, 4 plus mesna dose ≥ 60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.	Olaratumab 20 mg/kg + Doxorubicin + Ifosfamide Participants received olaratumab 20 mg/kg loading dose on days 1, 8 of cycle 1. From cycle 2, they received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m\^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m\^2 per day on days 1, 2, 3, 4 plus mesna dose ≥60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.
Overall Study STARTED	16	8
Overall Study Received at Least 1 Dose of Study Drug	16	8
Overall Study COMPLETED	9	2
Overall Study NOT COMPLETED	7	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Olaratumab 15 mg/kg + Doxorubicin + Ifosfamide Participants received olaratumab 15 milligrams per kilogram (mg/kg) on days 1, 8 plus doxorubicin 25 milligrams per meter square (mg/m\^2) on days 1, 2, 3 plus ifosfamide 2.5 gram per meter square (g/m\^2) per day on days 1, 2, 3, 4 plus mesna dose ≥ 60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.	Olaratumab 20 mg/kg + Doxorubicin + Ifosfamide Participants received olaratumab 20 mg/kg loading dose on days 1, 8 of cycle 1. From cycle 2, they received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m\^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m\^2 per day on days 1, 2, 3, 4 plus mesna dose ≥60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.
Overall Study Physician Decision	5	6
Overall Study Withdrawal by Subject	2	0

Baseline Characteristics

A Study of Olaratumab (LY3012207), Doxorubicin, and Ifosfamide in Participants With Advanced or Metastatic Soft Tissue Sarcoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Olaratumab 15 mg/kg + Doxorubicin + Ifosfamide n=16 Participants Participants received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m\^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m\^2 per day on days 1, 2, 3, 4 plus mesna dose ≥ 60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.	Olaratumab 20 mg/kg + Doxorubicin + Ifosfamide n=8 Participants Participants received olaratumab 20 mg/kg loading dose on days 1, 8 of cycle 1. From cycle 2, they received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m\^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m\^2 per day on days 1, 2, 3, 4 plus mesna dose ≥60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.	Total n=24 Participants Total of all reporting groups
Age, Continuous	42.6 years STANDARD_DEVIATION 11.1 • n=5 Participants	49.8 years STANDARD_DEVIATION 11.1 • n=7 Participants	45.0 years STANDARD_DEVIATION 11.4 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	5 Participants n=7 Participants	14 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	3 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	7 Participants n=5 Participants	1 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	15 Participants n=5 Participants	8 Participants n=7 Participants	23 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	6 participants n=5 Participants	5 participants n=7 Participants	11 participants n=5 Participants
Region of Enrollment Italy	3 participants n=5 Participants	0 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment Germany	7 participants n=5 Participants	3 participants n=7 Participants	10 participants n=5 Participants

PRIMARY outcome

Timeframe: Cycle 1 (Up To 24 days)

Population: All participants who received at least one dose of study drug.

Outcome measures

Outcome measures
Measure	Olaratumab 15 mg/kg + Doxorubicin + Ifosfamide n=16 Participants Participants received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m\^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m\^2 per day on days 1, 2, 3, 4 plus mesna dose ≥ 60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.	Olaratumab 20 mg/kg + Doxorubicin + Ifosfamide n=8 Participants Participants received olaratumab 20 mg/kg loading dose on days 1, 8 of cycle 1. From cycle 2, they received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m\^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m\^2 per day on days 1, 2, 3, 4 plus mesna dose ≥60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.
Number of Participants With Olaratumab Dose Limiting Toxicities (DLTs)	4 Participants	4 Participants

SECONDARY outcome

Timeframe: Cycle 1 - Day 1 (predose, end of infusion, 2 hours post olaratumab (olara), 6 hours post olara, 24 hours post olara, 72 hours post olara), Day 8 (predose, end of infusion, 2 hours post-olara, 6 hours post olara, 48 hours post olara, 168 hours post olara)

Population: All participants who received at least one dose of study drug and had evaluable PK data.

PK: Cmax of olaratumab.

Outcome measures

Outcome measures
Measure	Olaratumab 15 mg/kg + Doxorubicin + Ifosfamide n=16 Participants Participants received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m\^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m\^2 per day on days 1, 2, 3, 4 plus mesna dose ≥ 60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.	Olaratumab 20 mg/kg + Doxorubicin + Ifosfamide n=8 Participants Participants received olaratumab 20 mg/kg loading dose on days 1, 8 of cycle 1. From cycle 2, they received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m\^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m\^2 per day on days 1, 2, 3, 4 plus mesna dose ≥60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.
Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Olaratumab Cycle 1 Day 1	408 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 25	508 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 27
Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Olaratumab Cycle 1 Day 8	452 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 28	671 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 24

SECONDARY outcome

Timeframe: Cycle 3 - Day 1 (predose, end of infusion, 2 hours post olara, 5 hours post olara, 24 hours post olara, 72 hours post olara), Day 8 (predose, end of infusion, 2 hours post-olara, 5 hours post olara, 48 hours post olara, 168 hours post olara)

Population: All participants who received at least one dose of study drug and had evaluable PK data.

PK: Cmax of olaratumab at steady-state.

Outcome measures

Outcome measures
Measure	Olaratumab 15 mg/kg + Doxorubicin + Ifosfamide n=16 Participants Participants received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m\^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m\^2 per day on days 1, 2, 3, 4 plus mesna dose ≥ 60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.	Olaratumab 20 mg/kg + Doxorubicin + Ifosfamide n=8 Participants Participants received olaratumab 20 mg/kg loading dose on days 1, 8 of cycle 1. From cycle 2, they received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m\^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m\^2 per day on days 1, 2, 3, 4 plus mesna dose ≥60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.
PK: Maximum Serum Concentration (Cmax,ss) of Olaratumab at Steady-state Cycle 3 Day 1	533 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 22	494 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 9
PK: Maximum Serum Concentration (Cmax,ss) of Olaratumab at Steady-state Cycle 3 Day 8	523 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 18	545 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 13

SECONDARY outcome

Population: All participants who received at least one dose of study drug and had evaluable PK data.

PK: Cmin of olaratumab.

Outcome measures

Outcome measures
Measure	Olaratumab 15 mg/kg + Doxorubicin + Ifosfamide n=16 Participants Participants received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m\^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m\^2 per day on days 1, 2, 3, 4 plus mesna dose ≥ 60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.	Olaratumab 20 mg/kg + Doxorubicin + Ifosfamide n=8 Participants Participants received olaratumab 20 mg/kg loading dose on days 1, 8 of cycle 1. From cycle 2, they received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m\^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m\^2 per day on days 1, 2, 3, 4 plus mesna dose ≥60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.
PK: Trough Serum Concentration (Cmin) Cycle 1 Day 1	87.3 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 40	140 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 45
PK: Trough Serum Concentration (Cmin) Cycle 1 Day 8	46.7 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 105	53.3 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 143

SECONDARY outcome

Population: All participants who received at least one dose of study drug and had evaluable PK data.

PK: Cmin of olaratumab at steady-state.

Outcome measures

Outcome measures
Measure	Olaratumab 15 mg/kg + Doxorubicin + Ifosfamide n=16 Participants Participants received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m\^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m\^2 per day on days 1, 2, 3, 4 plus mesna dose ≥ 60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.	Olaratumab 20 mg/kg + Doxorubicin + Ifosfamide n=8 Participants Participants received olaratumab 20 mg/kg loading dose on days 1, 8 of cycle 1. From cycle 2, they received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m\^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m\^2 per day on days 1, 2, 3, 4 plus mesna dose ≥60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.
PK: Trough Serum Concentration (Cmin,ss) of Olaratumab at Steady-state Cycle 3 Day 8	126 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 35	115 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 32
PK: Trough Serum Concentration (Cmin,ss) of Olaratumab at Steady-state Cycle 3 Day 1	154 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 26	177 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 17

SECONDARY outcome

Timeframe: Baseline through Follow-up (Up To 21 Months)

Population: All participants with an evaluable baseline and at least 1 post-baseline data for Anti-Olaratumab Antibodies.

Participants with treatment-emergent anti-drug antibody (TE ADA) positive were 1) a participant with a 4-fold (2 dilutions) increase over a positive baseline antibody titer; or 2) for a negative baseline titer, a participant with an increase from the baseline to a level of 1:20.

Outcome measures

Outcome measures
Measure	Olaratumab 15 mg/kg + Doxorubicin + Ifosfamide n=15 Participants Participants received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m\^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m\^2 per day on days 1, 2, 3, 4 plus mesna dose ≥ 60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.	Olaratumab 20 mg/kg + Doxorubicin + Ifosfamide n=8 Participants Participants received olaratumab 20 mg/kg loading dose on days 1, 8 of cycle 1. From cycle 2, they received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m\^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m\^2 per day on days 1, 2, 3, 4 plus mesna dose ≥60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.
Number of Participants With Anti-Olaratumab Antibodies	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline up to Short-Term Follow-Up Period (Up To 21 Months)

Population: All participants who received at least one dose of study drug.

Objective response rate is the best overall tumor response of complete response (CR) or partial response (PR) as classified by the independent central review according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions.

Outcome measures

Outcome measures
Measure	Olaratumab 15 mg/kg + Doxorubicin + Ifosfamide n=16 Participants Participants received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m\^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m\^2 per day on days 1, 2, 3, 4 plus mesna dose ≥ 60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.	Olaratumab 20 mg/kg + Doxorubicin + Ifosfamide n=8 Participants Participants received olaratumab 20 mg/kg loading dose on days 1, 8 of cycle 1. From cycle 2, they received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m\^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m\^2 per day on days 1, 2, 3, 4 plus mesna dose ≥60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.
Objective Response Rate (ORR): Number of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR)	6 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline to Objective Disease Progression or Death Due to Any Cause (Up To 21 Months)

Population: All participants who received at least one dose of study drug. Number of participants censored were Olaratumab 15 mg/kg + Doxorubicin + Ifosfamide = 8 and Olaratumab 20 mg/kg + Doxorubicin + Ifosfamide = 6.

Progression-free survival time was measured from randomization until the date of objective progression as defined by Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1), or death from any cause. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Participants who have neither progressed nor died were censored at the day of their last radiographic tumor assessment, if available, or date of randomization if no post-baseline radiographic assessment is available.

Outcome measures

Outcome measures
Measure	Olaratumab 15 mg/kg + Doxorubicin + Ifosfamide n=16 Participants Participants received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m\^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m\^2 per day on days 1, 2, 3, 4 plus mesna dose ≥ 60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.	Olaratumab 20 mg/kg + Doxorubicin + Ifosfamide n=8 Participants Participants received olaratumab 20 mg/kg loading dose on days 1, 8 of cycle 1. From cycle 2, they received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m\^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m\^2 per day on days 1, 2, 3, 4 plus mesna dose ≥60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.
Progression Free Survival (PFS)	9.53 Months Interval 4.07 to 14.29	6.93 Months Interval 1.28 to 6.93

SECONDARY outcome

Timeframe: Date of Complete Response (CR) or Partial Response (PR) to Objective Disease Progression or Death Due to Any Cause (Up To 21 Months)

Population: All participants who received at least one dose of study drug. Number of participants censored were Olaratumab 15 mg/kg + Doxorubicin + Ifosfamide = 4 and Olaratumab 20 mg/kg + Doxorubicin + Ifosfamide = 1.

Duration of response is defined as the time from the date measurement criteria for CR or PR (whichever is first recorded) are first met until the first date that disease is recurrent or objective progression is observed, per RECIST 1.1, or the date of death from any cause in the absence of objectively determined disease progression or recurrence. Participants known to be alive and without disease progression will be censored at the time of the last adequate tumor assessment.

Outcome measures

Outcome measures
Measure	Olaratumab 15 mg/kg + Doxorubicin + Ifosfamide n=16 Participants Participants received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m\^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m\^2 per day on days 1, 2, 3, 4 plus mesna dose ≥ 60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.	Olaratumab 20 mg/kg + Doxorubicin + Ifosfamide n=8 Participants Participants received olaratumab 20 mg/kg loading dose on days 1, 8 of cycle 1. From cycle 2, they received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m\^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m\^2 per day on days 1, 2, 3, 4 plus mesna dose ≥60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.
Duration of Response (DoR)	8.25 Months Interval 8.15 to 8.34	NA Months Values not attained due to high censoring rate.

SECONDARY outcome

Timeframe: Baseline until Disease Progression or Death Due to Any Cause (Up To 21 Months)

Population: All participants who received at least one dose of study drug.

Disease control rate (DCR) is the percentage of participants with a best overall response of CR, PR or SD as defined by RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

Outcome measures

Outcome measures
Measure	Olaratumab 15 mg/kg + Doxorubicin + Ifosfamide n=16 Participants Participants received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m\^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m\^2 per day on days 1, 2, 3, 4 plus mesna dose ≥ 60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.	Olaratumab 20 mg/kg + Doxorubicin + Ifosfamide n=8 Participants Participants received olaratumab 20 mg/kg loading dose on days 1, 8 of cycle 1. From cycle 2, they received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m\^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m\^2 per day on days 1, 2, 3, 4 plus mesna dose ≥60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.
Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD)	81.3 Percentage of participants	87.5 Percentage of participants

SECONDARY outcome

Timeframe: Baseline to Date of Death Due to Any Cause (Up To 21 Months)

Population: All participants who received at least one dose of study drug. Number of participants censored were Olaratumab 15 mg/kg + Doxorubicin + Ifosfamide = 9 and Olaratumab 20 mg/kg + Doxorubicin + Ifosfamide = 6.

Overall survival is defined as the time from the date of randomization to the date of death from any cause. For each participant who is not known to have died as of the data-inclusion cut-off date for a particular analysis, overall survival duration was censored for that analysis at the date of last prior contact.

Outcome measures

Outcome measures
Measure	Olaratumab 15 mg/kg + Doxorubicin + Ifosfamide n=16 Participants Participants received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m\^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m\^2 per day on days 1, 2, 3, 4 plus mesna dose ≥ 60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.	Olaratumab 20 mg/kg + Doxorubicin + Ifosfamide n=8 Participants Participants received olaratumab 20 mg/kg loading dose on days 1, 8 of cycle 1. From cycle 2, they received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m\^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m\^2 per day on days 1, 2, 3, 4 plus mesna dose ≥60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.
Overall Survival (OS)	16.72 Months Interval 8.38 to Values not attained due to high censoring rate.	NA Months Interval 1.28 to Values not attained due to high censoring rate.

Adverse Events

Olaratumab 15 mg/kg + Doxorubicin + Ifosfamide

Serious events: 9 serious events

Other events: 16 other events

Deaths: 7 deaths

Olaratumab 20 mg/kg + Doxorubicin + Ifosfamide

Serious events: 7 serious events

Other events: 8 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Olaratumab 15 mg/kg + Doxorubicin + Ifosfamide n=16 participants at risk Participants received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m\^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m\^2 per day on days 1, 2, 3, 4 plus mesna dose ≥ 60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.	Olaratumab 20 mg/kg + Doxorubicin + Ifosfamide n=8 participants at risk Participants received olaratumab 20 mg/kg loading dose on days 1, 8 of cycle 1. From cycle 2, they received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m\^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m\^2 per day on days 1, 2, 3, 4 plus mesna dose ≥60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.
Blood and lymphatic system disorders Anaemia	12.5% 2/16 • Number of events 5 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.	12.5% 1/8 • Number of events 1 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
Blood and lymphatic system disorders Febrile neutropenia	37.5% 6/16 • Number of events 8 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.	50.0% 4/8 • Number of events 6 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
Blood and lymphatic system disorders Neutropenia	6.2% 1/16 • Number of events 1 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/8 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
Cardiac disorders Atrial fibrillation	0.00% 0/16 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.	12.5% 1/8 • Number of events 1 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
Gastrointestinal disorders Haemorrhoids	6.2% 1/16 • Number of events 1 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/8 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
Gastrointestinal disorders Nausea	6.2% 1/16 • Number of events 1 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/8 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
Gastrointestinal disorders Oesophagitis	6.2% 1/16 • Number of events 1 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/8 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
Gastrointestinal disorders Vomiting	6.2% 1/16 • Number of events 1 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/8 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
General disorders Fatigue	12.5% 2/16 • Number of events 2 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/8 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
General disorders Mucosal inflammation	6.2% 1/16 • Number of events 1 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/8 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
Infections and infestations Device related infection	6.2% 1/16 • Number of events 1 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/8 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
Infections and infestations Pneumonia	0.00% 0/16 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.	25.0% 2/8 • Number of events 2 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
Injury, poisoning and procedural complications Fracture	0.00% 0/16 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.	12.5% 1/8 • Number of events 1 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
Investigations Blood creatinine increased	0.00% 0/16 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.	12.5% 1/8 • Number of events 1 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
Investigations Platelet count decreased	12.5% 2/16 • Number of events 2 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.	25.0% 2/8 • Number of events 3 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
Investigations White blood cell count decreased	0.00% 0/16 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.	12.5% 1/8 • Number of events 1 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
Metabolism and nutrition disorders Dehydration	6.2% 1/16 • Number of events 1 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/8 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
Metabolism and nutrition disorders Hyponatraemia	6.2% 1/16 • Number of events 1 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/8 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
Musculoskeletal and connective tissue disorders Muscular weakness	6.2% 1/16 • Number of events 1 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/8 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic neoplasm	6.2% 1/16 • Number of events 1 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/8 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	6.2% 1/16 • Number of events 1 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/8 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	6.2% 1/16 • Number of events 1 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/8 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
Product Issues Device dislocation	0.00% 0/16 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.	12.5% 1/8 • Number of events 1 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	6.2% 1/16 • Number of events 1 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/8 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
Vascular disorders Haemodynamic instability	6.2% 1/16 • Number of events 1 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/8 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
Vascular disorders Hypotension	6.2% 1/16 • Number of events 1 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/8 • Up To 2 years All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.