Trial Outcomes & Findings for A Study of Olaratumab in Japanese Participants With Advanced Cancer (NCT NCT02377752)

Last Updated: 2021-02-17

Results Overview

Clinically significant events were defined as serious adverse events (SAE). A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

25 participants

Primary outcome timeframe

Baseline to Study completion (Up To 3.5 Years)

Results posted on

2021-02-17

Participant Flow

Participants were considered to have competed the study if the study discontinued due to adverse event, progressive disease (PD) or withdrawal by subject.

Participant milestones

Participant milestones
Measure	Part A Cohort 1: Olaratumab+Doxorubicin 15 milligram per kilogram (mg/kg) of olaratumab administered intravenously (IV) on Day 1 and Day 8, and 25 milligram per square meter (mg/m2) of doxorubicin administered IV on Day 1, Day 2, and Day 3 every 21-day cycle for up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met	Part A Cohort 2: Olaratumab+Doxorubicin 15 mg/kg of olaratumab administered IV on Day 1 and Day 8, and 75 mg/m2 of doxorubicin administered IV on Day 1 every 21 day-cycle for up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Part A Cohort 3 Olaratumab + Doxorubicin 20 mg/kg loading dose of olaratumab administered IV on Day 1 and Day 8 in Cycle 1, followed by 15 mg/kg IV on Day 1 and Day 8 in subsequent cycles, and 75 mg/m2 of doxorubicin administered IV on Day 1 of every 21 day-cycle up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Part B: Olaratumab 15 mg/kg olaratumab administered IV on Day 1 and Day 8 of every 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Overall Study STARTED	7	6	6	6
Overall Study Received at Least 1 Dose of Study Drug	7	6	6	6
Overall Study COMPLETED	7	6	6	6
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study of Olaratumab in Japanese Participants With Advanced Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A Cohort 1: Olaratumab+Doxorubicin n=7 Participants 15 mg/kg of olaratumab administered IV on Day 1 and Day 8, and 25 mg/m2 of doxorubicin administered IV on Day 1, Day 2, and Day 3 every 21-day cycle for up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Part A Cohort 2: Olaratumab+Doxorubicin n=6 Participants 15 mg/kg of olaratumab administered IV on Day 1 and Day 8, and 75 mg/m2 of doxorubicin administered IV on Day 1 every 21 day-cycle for up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Part A Cohort 3 Olaratumab + Doxorubicin n=6 Participants 20 mg/kg loading dose of olaratumab administered IV on Day 1 and Day 8 in Cycle 1, followed by 15 mg/kg IV on Day 1 and Day 8 in subsequent cycles, and 75 mg/m2 of doxorubicin administered IV on Day 1 of every 21 day-cycle up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Part B: Olaratumab n=6 Participants 15 mg/kg olaratumab administered IV on Day 1 and Day 8 of every 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.	Total n=25 Participants Total of all reporting groups
Age, Continuous	50.1 years STANDARD_DEVIATION 15.3 • n=5 Participants	45.8 years STANDARD_DEVIATION 11.0 • n=7 Participants	40.7 years STANDARD_DEVIATION 8.7 • n=5 Participants	59.3 years STANDARD_DEVIATION 8.1 • n=4 Participants	49.0 years STANDARD_DEVIATION 12.7 • n=21 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	5 Participants n=4 Participants	16 Participants n=21 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	9 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	7 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	6 Participants n=4 Participants	25 Participants n=21 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	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Region of Enrollment Japan	7 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	6 Participants n=4 Participants	25 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline to Study completion (Up To 3.5 Years)

Population: All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A.

Outcome measures

Outcome measures
Measure	Part A Cohort 1: Olaratumab+Doxorubicin n=7 Participants 15 mg/kg of olaratumab administered IV on Day 1 and Day 8, and 25 mg/m2 of doxorubicin administered IV on Day 1, Day 2, and Day 3 every 21-day cycle for up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Part A Cohort 2: Olaratumab+Doxorubicin n=6 Participants 15 mg/kg of olaratumab administered IV on Day 1 and Day 8, and 75 mg/m2 of doxorubicin administered IV on Day 1 every 21 day-cycle for up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Part A Cohort 3 Olaratumab + Doxorubicin n=6 Participants 20 mg/kg loading dose of olaratumab administered IV on Day 1 and Day 8 in Cycle 1, followed by 15 mg/kg IV on Day 1 and Day 8 in subsequent cycles, and 75 mg/m2 of doxorubicin administered IV on Day 1 of every 21 day-cycle up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Part B: Olaratumab 15 mg/kg olaratumab administered IV on Day 1 and Day 8 of every 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Part A: Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration	1 participants	4 participants	1 participants	—

PRIMARY outcome

Timeframe: Cycle 1 (21 Days)

Population: All enrolled patients who completed Cycle 1 (initial 21-day treatment period), or who discontinued due to DLT during Cycle 1 in Part A.

DLT is defined as adverse event (AE) during Cycle 1 (Days 1 through 21) that was possibly related to the study drug and toxicities considered by the investigator as dose limiting. A summary of other nonserious AEs, and all serious adverse events (SAE's), regardless of causality, is located in the Reported Adverse Events section.

Outcome measures

Outcome measures
Measure	Part A Cohort 1: Olaratumab+Doxorubicin n=7 Participants 15 mg/kg of olaratumab administered IV on Day 1 and Day 8, and 25 mg/m2 of doxorubicin administered IV on Day 1, Day 2, and Day 3 every 21-day cycle for up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Part A Cohort 2: Olaratumab+Doxorubicin n=6 Participants 15 mg/kg of olaratumab administered IV on Day 1 and Day 8, and 75 mg/m2 of doxorubicin administered IV on Day 1 every 21 day-cycle for up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Part A Cohort 3 Olaratumab + Doxorubicin n=6 Participants 20 mg/kg loading dose of olaratumab administered IV on Day 1 and Day 8 in Cycle 1, followed by 15 mg/kg IV on Day 1 and Day 8 in subsequent cycles, and 75 mg/m2 of doxorubicin administered IV on Day 1 of every 21 day-cycle up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Part B: Olaratumab 15 mg/kg olaratumab administered IV on Day 1 and Day 8 of every 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Part A: Number of Participants With Dose Limiting Toxicities (DLTs)	0 Participants	1 Participants	0 Participants	—

PRIMARY outcome

Timeframe: Cycle (C) 1 Day (D) 1 and C3 D1: Pre-infusion, Immediately postinfusion and 1, 24, 48, 72 and 168 hours (h) postinfusion; C1 D8 and C3 D8: Pre- infusion, Immediately postinfusion and 1, 48, 72, 168 and 336 h postinfusion

Population: All enrolled participants who received any amount of study drug (olaratumab) and had evaluable pharmacokinetics (PK) data in Part B.

Maximum observed serum concentration (Cmax) of olaratumab is reported.

Outcome measures

Outcome measures
Measure	Part A Cohort 1: Olaratumab+Doxorubicin n=6 Participants 15 mg/kg of olaratumab administered IV on Day 1 and Day 8, and 25 mg/m2 of doxorubicin administered IV on Day 1, Day 2, and Day 3 every 21-day cycle for up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Part A Cohort 2: Olaratumab+Doxorubicin 15 mg/kg of olaratumab administered IV on Day 1 and Day 8, and 75 mg/m2 of doxorubicin administered IV on Day 1 every 21 day-cycle for up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Part A Cohort 3 Olaratumab + Doxorubicin 20 mg/kg loading dose of olaratumab administered IV on Day 1 and Day 8 in Cycle 1, followed by 15 mg/kg IV on Day 1 and Day 8 in subsequent cycles, and 75 mg/m2 of doxorubicin administered IV on Day 1 of every 21 day-cycle up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Part B: Olaratumab 15 mg/kg olaratumab administered IV on Day 1 and Day 8 of every 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Part B: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Olaratumab Cycle 1 Day 1	322 microgram per milliliter (μg/mL) Geometric Coefficient of Variation 22	—	—	—
Part B: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Olaratumab Cycle 1 Day 8	409 microgram per milliliter (μg/mL) Geometric Coefficient of Variation 32	—	—	—
Part B: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Olaratumab Cycle 3 Day 1	396 microgram per milliliter (μg/mL) Geometric Coefficient of Variation 16	—	—	—
Part B: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Olaratumab Cycle 3 Day 8	478 microgram per milliliter (μg/mL) Geometric Coefficient of Variation 15	—	—	—

PRIMARY outcome

Population: All enrolled participants who received any amount of study drug (olaratumab) and had evaluable PK data in Part B.

AUC(0-t) hours (h), area under the serum concentration versus time curve from time zero to t hours at AUC(0-168h) for Cycle 1 Day 1 and Cycle 3 Day 1, AUC(0-336h) for Cycle 1 Day 8 and Cycle 3 Day 8 of Olaratumab is reported.

Outcome measures

Outcome measures
Measure	Part A Cohort 1: Olaratumab+Doxorubicin n=6 Participants 15 mg/kg of olaratumab administered IV on Day 1 and Day 8, and 25 mg/m2 of doxorubicin administered IV on Day 1, Day 2, and Day 3 every 21-day cycle for up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Part A Cohort 2: Olaratumab+Doxorubicin 15 mg/kg of olaratumab administered IV on Day 1 and Day 8, and 75 mg/m2 of doxorubicin administered IV on Day 1 every 21 day-cycle for up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Part A Cohort 3 Olaratumab + Doxorubicin 20 mg/kg loading dose of olaratumab administered IV on Day 1 and Day 8 in Cycle 1, followed by 15 mg/kg IV on Day 1 and Day 8 in subsequent cycles, and 75 mg/m2 of doxorubicin administered IV on Day 1 of every 21 day-cycle up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Part B: Olaratumab 15 mg/kg olaratumab administered IV on Day 1 and Day 8 of every 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Part B: Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of Olaratumab Cycle 1 Day 1: AUC(0-168h)	23300 microgramhour/mL (μgh/mL) Geometric Coefficient of Variation 26	—	—	—
Part B: Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of Olaratumab Cycle 1 Day 8: AUC(0-336h)	48100 microgramhour/mL (μgh/mL) Geometric Coefficient of Variation 47	—	—	—
Part B: Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of Olaratumab Cycle 3 Day 1: AUC(0-168h)	39800 microgramhour/mL (μgh/mL) Geometric Coefficient of Variation 14	—	—	—
Part B: Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of Olaratumab Cycle 3 Day 8: AUC(0-336h)	NA microgramhour/mL (μgh/mL) Geometric Coefficient of Variation NA NA = Data reported as individual values when participants analyzed (n) were less than 3. Individual values of AUC(0-336h) = 66500 μg\h/mL, 92300 μg\h/mL.	—	—	—

SECONDARY outcome

Timeframe: Cycle (C) 1 Day (D) 1 and C3 D1: Pre-infusion, Immediately postinfusion and 1.5, 24, 48, 72 and 168 hours (h) postinfusion; C1 D8 and C3 D8: Pre- infusion, Immediately postinfusion and 1, 48, 72, 168 and 336 h postinfusion

Population: All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) and had evaluable PK data in Part A.

Maximum observed serum concentration (Cmax) of olaratumab is reported.

Outcome measures

Outcome measures
Measure	Part A Cohort 1: Olaratumab+Doxorubicin n=6 Participants 15 mg/kg of olaratumab administered IV on Day 1 and Day 8, and 25 mg/m2 of doxorubicin administered IV on Day 1, Day 2, and Day 3 every 21-day cycle for up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Part A Cohort 2: Olaratumab+Doxorubicin n=6 Participants 15 mg/kg of olaratumab administered IV on Day 1 and Day 8, and 75 mg/m2 of doxorubicin administered IV on Day 1 every 21 day-cycle for up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Part A Cohort 3 Olaratumab + Doxorubicin n=6 Participants 20 mg/kg loading dose of olaratumab administered IV on Day 1 and Day 8 in Cycle 1, followed by 15 mg/kg IV on Day 1 and Day 8 in subsequent cycles, and 75 mg/m2 of doxorubicin administered IV on Day 1 of every 21 day-cycle up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Part B: Olaratumab 15 mg/kg olaratumab administered IV on Day 1 and Day 8 of every 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Part A: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Olaratumab Cycle 1 Day 1	274 microgram per milliliter (μg/mL) Geometric Coefficient of Variation 30	301 microgram per milliliter (μg/mL) Geometric Coefficient of Variation 25	470 microgram per milliliter (μg/mL) Geometric Coefficient of Variation 27	—
Part A: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Olaratumab Cycle 1 Day 8	353 microgram per milliliter (μg/mL) Geometric Coefficient of Variation 40	351 microgram per milliliter (μg/mL) Geometric Coefficient of Variation 20	610 microgram per milliliter (μg/mL) Geometric Coefficient of Variation 33	—
Part A: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Olaratumab Cycle 3 Day 1	351 microgram per milliliter (μg/mL) Geometric Coefficient of Variation 28	390 microgram per milliliter (μg/mL) Geometric Coefficient of Variation 13	545 microgram per milliliter (μg/mL) Geometric Coefficient of Variation 34	—
Part A: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Olaratumab Cycle 3 Day 8	415 microgram per milliliter (μg/mL) Geometric Coefficient of Variation 28	474 microgram per milliliter (μg/mL) Geometric Coefficient of Variation 13	541 microgram per milliliter (μg/mL) Geometric Coefficient of Variation 41	—

SECONDARY outcome

Population: All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) and had evaluable PK data in Part A.

Outcome measures

Outcome measures
Measure	Part A Cohort 1: Olaratumab+Doxorubicin n=6 Participants 15 mg/kg of olaratumab administered IV on Day 1 and Day 8, and 25 mg/m2 of doxorubicin administered IV on Day 1, Day 2, and Day 3 every 21-day cycle for up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Part A Cohort 2: Olaratumab+Doxorubicin n=6 Participants 15 mg/kg of olaratumab administered IV on Day 1 and Day 8, and 75 mg/m2 of doxorubicin administered IV on Day 1 every 21 day-cycle for up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Part A Cohort 3 Olaratumab + Doxorubicin n=6 Participants 20 mg/kg loading dose of olaratumab administered IV on Day 1 and Day 8 in Cycle 1, followed by 15 mg/kg IV on Day 1 and Day 8 in subsequent cycles, and 75 mg/m2 of doxorubicin administered IV on Day 1 of every 21 day-cycle up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Part B: Olaratumab 15 mg/kg olaratumab administered IV on Day 1 and Day 8 of every 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Part A: Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of Olaratumab Cycle 1 Day 1: AUC(0-168h)	21700 microgramhour per milliliter (μgh/mL) Geometric Coefficient of Variation 36	21900 microgramhour per milliliter (μgh/mL) Geometric Coefficient of Variation 25	34300 microgramhour per milliliter (μgh/mL) Geometric Coefficient of Variation 29	—
Part A: Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of Olaratumab Cycle 1 Day 8: AUC(0-336h)	47300 microgramhour per milliliter (μgh/mL) Geometric Coefficient of Variation 32	42000 microgramhour per milliliter (μgh/mL) Geometric Coefficient of Variation 36	74100 microgramhour per milliliter (μgh/mL) Geometric Coefficient of Variation 42	—
Part A: Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of Olaratumab Cycle 3 Day 1: AUC(0-168h)	33600 microgramhour per milliliter (μgh/mL) Geometric Coefficient of Variation 31	36000 microgramhour per milliliter (μgh/mL) Geometric Coefficient of Variation 15	42500 microgramhour per milliliter (μgh/mL) Geometric Coefficient of Variation 51	—
Part A: Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of Olaratumab Cycle 3 Day 8: AUC(0-336h)	63000 microgramhour per milliliter (μgh/mL) Geometric Coefficient of Variation 28	68400 microgramhour per milliliter (μgh/mL) Geometric Coefficient of Variation 15	77700 microgramhour per milliliter (μgh/mL) Geometric Coefficient of Variation 68	—

SECONDARY outcome

Timeframe: Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 3, Cycle 3 Day 1, Cycle 3 Day 2 and Cycle 3 Day 3: Immediately postinfusion

Population: All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) and had evaluable PK data in Part A.

Maximum observed plasma concentration (Cmax) of doxorubicin is reported.

Outcome measures

Outcome measures
Measure	Part A Cohort 1: Olaratumab+Doxorubicin n=6 Participants 15 mg/kg of olaratumab administered IV on Day 1 and Day 8, and 25 mg/m2 of doxorubicin administered IV on Day 1, Day 2, and Day 3 every 21-day cycle for up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Part A Cohort 2: Olaratumab+Doxorubicin 15 mg/kg of olaratumab administered IV on Day 1 and Day 8, and 75 mg/m2 of doxorubicin administered IV on Day 1 every 21 day-cycle for up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Part A Cohort 3 Olaratumab + Doxorubicin 20 mg/kg loading dose of olaratumab administered IV on Day 1 and Day 8 in Cycle 1, followed by 15 mg/kg IV on Day 1 and Day 8 in subsequent cycles, and 75 mg/m2 of doxorubicin administered IV on Day 1 of every 21 day-cycle up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Part B: Olaratumab 15 mg/kg olaratumab administered IV on Day 1 and Day 8 of every 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Part A: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Doxorubicin Cycle 1 Day 1	594 nanogram/milliliter (ng/mL Geometric Coefficient of Variation 86	—	—	—
Part A: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Doxorubicin Cycle 1 Day 2	444 nanogram/milliliter (ng/mL Geometric Coefficient of Variation 97	—	—	—
Part A: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Doxorubicin Cycle 1 Day 3	384 nanogram/milliliter (ng/mL Geometric Coefficient of Variation 105	—	—	—
Part A: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Doxorubicin Cycle 3 Day 1	855 nanogram/milliliter (ng/mL Geometric Coefficient of Variation 29	—	—	—
Part A: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Doxorubicin Cycle 3 Day 2	742 nanogram/milliliter (ng/mL Geometric Coefficient of Variation 45	—	—	—
Part A: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Doxorubicin Cycle 3 Day 3	884 nanogram/milliliter (ng/mL Geometric Coefficient of Variation 24	—	—	—

SECONDARY outcome

Timeframe: Cycle 1 Day 1 and Cycle 3 Day 1: Immediately postinfusion, 0.5, 1, 2, 4, 8, 24, 48, and 72 h postinfusion

Population: All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) and had evaluable PK data in Part A.

Maximum observed plasma concentration (Cmax) of doxorubicin is reported.

Outcome measures

Outcome measures
Measure	Part A Cohort 1: Olaratumab+Doxorubicin n=6 Participants 15 mg/kg of olaratumab administered IV on Day 1 and Day 8, and 25 mg/m2 of doxorubicin administered IV on Day 1, Day 2, and Day 3 every 21-day cycle for up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Part A Cohort 2: Olaratumab+Doxorubicin n=6 Participants 15 mg/kg of olaratumab administered IV on Day 1 and Day 8, and 75 mg/m2 of doxorubicin administered IV on Day 1 every 21 day-cycle for up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Part A Cohort 3 Olaratumab + Doxorubicin 20 mg/kg loading dose of olaratumab administered IV on Day 1 and Day 8 in Cycle 1, followed by 15 mg/kg IV on Day 1 and Day 8 in subsequent cycles, and 75 mg/m2 of doxorubicin administered IV on Day 1 of every 21 day-cycle up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Part B: Olaratumab 15 mg/kg olaratumab administered IV on Day 1 and Day 8 of every 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Part A: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Doxorubicin Cycle 1 Day 1	2660 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 25	2790 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 12	—	—
Part A: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Doxorubicin Cycle 3 Day 1	NA nanogram/milliliter (ng/mL) Geometric Coefficient of Variation NA NA = Data reported as individual values when participants analyzed (n) were less than 3. Individual values of Cmax = 1791.71 ng/mL, 1812.61 ng/mL.	2900 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 19	—	—

SECONDARY outcome

Timeframe: Cycle 1 Day 1 and Cycle 3 Day 1: Immediately postinfusion, 0.5, 1, 2, 4, 8, 24, 48, and 72 h postinfusion

Population: All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) and had evaluable PK data in Part A. AUC data is not available for Part A cohort 1 as PK was evaluated immediately post infusion of doxorubicin in Part A cohort 1.

Area under the concentration verses time curve from zero to infinity (AUC\[0-∞\]) of doxorubicin is reported.

Outcome measures

Outcome measures
Measure	Part A Cohort 1: Olaratumab+Doxorubicin n=6 Participants 15 mg/kg of olaratumab administered IV on Day 1 and Day 8, and 25 mg/m2 of doxorubicin administered IV on Day 1, Day 2, and Day 3 every 21-day cycle for up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Part A Cohort 2: Olaratumab+Doxorubicin n=6 Participants 15 mg/kg of olaratumab administered IV on Day 1 and Day 8, and 75 mg/m2 of doxorubicin administered IV on Day 1 every 21 day-cycle for up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Part A Cohort 3 Olaratumab + Doxorubicin 20 mg/kg loading dose of olaratumab administered IV on Day 1 and Day 8 in Cycle 1, followed by 15 mg/kg IV on Day 1 and Day 8 in subsequent cycles, and 75 mg/m2 of doxorubicin administered IV on Day 1 of every 21 day-cycle up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Part B: Olaratumab 15 mg/kg olaratumab administered IV on Day 1 and Day 8 of every 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Part A: Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of Doxorubicin Cycle 1 Day 1	3070 nanogramhour/mL (ngh/mL) Geometric Coefficient of Variation 12	3020 nanogramhour/mL (ngh/mL) Geometric Coefficient of Variation 15	—	—
Part A: Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of Doxorubicin Cycle 3 Day 1	NA nanogramhour/mL (ngh/mL) Geometric Coefficient of Variation NA NA = Data reported as individual values when participants analyzed (n) were less than 3. Individual values of AUC\[0-∞\] = 2990 ng\h/mL, 3410 ng\h/mL.	3720 nanogramhour/mL (ngh/mL) Geometric Coefficient of Variation 17	—	—

SECONDARY outcome

Timeframe: Baseline to Study completion (Up To 3.5 Years)

Population: All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.

Tumor response was assessed according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1. Complete Response (CR) is disappearance of all target lesions; Partial Response (PR) is greater than or equal to (≥) 30% decrease in sum of longest diameter of target lesions.

Outcome measures

Outcome measures
Measure	Part A Cohort 1: Olaratumab+Doxorubicin n=7 Participants 15 mg/kg of olaratumab administered IV on Day 1 and Day 8, and 25 mg/m2 of doxorubicin administered IV on Day 1, Day 2, and Day 3 every 21-day cycle for up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Part A Cohort 2: Olaratumab+Doxorubicin n=6 Participants 15 mg/kg of olaratumab administered IV on Day 1 and Day 8, and 75 mg/m2 of doxorubicin administered IV on Day 1 every 21 day-cycle for up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Part A Cohort 3 Olaratumab + Doxorubicin n=6 Participants 20 mg/kg loading dose of olaratumab administered IV on Day 1 and Day 8 in Cycle 1, followed by 15 mg/kg IV on Day 1 and Day 8 in subsequent cycles, and 75 mg/m2 of doxorubicin administered IV on Day 1 of every 21 day-cycle up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Part B: Olaratumab n=6 Participants 15 mg/kg olaratumab administered IV on Day 1 and Day 8 of every 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Change From Baseline in Percentage of Participants With a Tumor Response	0 percentage of participants Interval 0.0 to 35.4	33.3 percentage of participants Interval 9.7 to 70.0	33.3 percentage of participants Interval 9.7 to 70.0	0 percentage of participants Interval 0.0 to 39.0

Adverse Events

Part A Cohort 1: Olaratumab+Doxorubicin

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Part A Cohort 2: Olaratumab+Doxorubicin

Serious events: 4 serious events

Other events: 6 other events

Deaths: 0 deaths

Part A Cohort 3 Olaratumab + Doxorubicin

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Part B: Olaratumab

Serious events: 2 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Part A Cohort 1: Olaratumab+Doxorubicin n=7 participants at risk 15 mg/kg of olaratumab administered IV on Day 1 and Day 8, and 25 mg/m2 of doxorubicin administered IV on Day 1, Day 2, and Day 3 every 21-day cycle for up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Part A Cohort 2: Olaratumab+Doxorubicin n=6 participants at risk 15 mg/kg of olaratumab administered IV on Day 1 and Day 8, and 75 mg/m2 of doxorubicin administered IV on Day 1 every 21 day-cycle for up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Part A Cohort 3 Olaratumab + Doxorubicin n=6 participants at risk 20 mg/kg loading dose of olaratumab administered IV on Day 1 and Day 8 in Cycle 1, followed by 15 mg/kg IV on Day 1 and Day 8 in subsequent cycles, and 75 mg/m2 of doxorubicin administered IV on Day 1 of every 21 day-cycle up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met.	Part B: Olaratumab n=6 participants at risk 15 mg/kg olaratumab administered IV on Day 1 and Day 8 of every 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/7 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.	16.7% 1/6 • Number of events 1 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.	16.7% 1/6 • Number of events 1 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.	0.00% 0/6 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.
Cardiac disorders Left ventricular dysfunction	0.00% 0/7 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.	16.7% 1/6 • Number of events 1 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.	0.00% 0/6 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.	0.00% 0/6 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.
Gastrointestinal disorders Ileus	0.00% 0/7 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.	0.00% 0/6 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.	0.00% 0/6 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.	16.7% 1/6 • Number of events 1 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/7 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.	16.7% 1/6 • Number of events 1 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.	0.00% 0/6 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.	0.00% 0/6 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.
Infections and infestations Lung infection	0.00% 0/7 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.	16.7% 1/6 • Number of events 1 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.	16.7% 1/6 • Number of events 1 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.	0.00% 0/6 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.
Infections and infestations Meningitis	0.00% 0/7 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.	16.7% 1/6 • Number of events 1 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.	0.00% 0/6 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.	0.00% 0/6 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.
Infections and infestations Pneumonia	0.00% 0/7 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.	0.00% 0/6 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.	0.00% 0/6 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.	16.7% 1/6 • Number of events 1 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.
Injury, poisoning and procedural complications Infusion related reaction	14.3% 1/7 • Number of events 1 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.	0.00% 0/6 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.	0.00% 0/6 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.	0.00% 0/6 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.
Investigations Neutrophil count decreased	0.00% 0/7 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.	33.3% 2/6 • Number of events 2 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.	0.00% 0/6 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.	0.00% 0/6 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.
Investigations Platelet count decreased	0.00% 0/7 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.	0.00% 0/6 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.	0.00% 0/6 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.	16.7% 1/6 • Number of events 1 • Baseline to Study completion (Up To 3.5 Years) All enrolled participants who received any amount of study drugs (either olaratumab or doxorubicin) in Part A and Part B.

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 Principal investigators are fully restricted to publish any results of the study without sponsor's permission.
Publication restrictions are in place

Restriction type: OTHER