Neoplasm
Conditions
Brief summary
This study consists of 2 parts (Part A and Part B). The main purpose of Part A is to evaluate safety and side effects of olaratumab in combination with doxorubicin in Japanese participants with a group of rare cancers (advanced solid tumors, especially advanced soft tissue sarcoma \[STS\].) The main purpose of Part B is to evaluate how much olaratumab gets into the blood stream of Japanese participants with advanced solid tumors and how long it takes the body to get rid of it.
Interventions
BIOLOGICALOlaratumab
Administered IV
DRUGDoxorubicin
Administered IV
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Part A: Have histological or cytological evidence of a diagnosis of advanced or metastatic solid tumor, especially STS, which is not amenable to treatment with surgery or radiotherapy. Part B: Have histological or cytological evidence of a diagnosis of solid tumor that is advanced or metastatic. * Have the presence of measurable or nonmeasurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST). * Have given written informed consent prior to any study-specific procedures. * Have adequate organ and coagulation function * Have an Eastern Cooperative Oncology Group (ECOG) performance score (PS) of less than or equal to 1. * Have discontinued previous treatments for cancer and recovered from the acute effects of therapy. * (Part A only) Have a prestudy echocardiogram with an actual left ventricular ejection fraction greater than or equal to 50%, within 21 days prior to first dose of study medication. * All participants agree to use a reliable method of birth control and to not donate sperm during the study and for at least 3 months following last dose of study drug. * Female participants: * must either be women not of child-bearing potential due to surgical sterilization confirmed by medical history, or menopause or * women of child-bearing potential who test negative for pregnancy within 7 days before the first dose of study drug based on serum or urine pregnancy test and agree not to breast feed during the study and for 3 months following the last dose of the study drug(s) * Have an estimated life expectancy of more than or equal to 3 months in the judgment of the investigator.
Exclusion criteria
* Have received treatment within 21 days of the initial dose of study drug with an investigational product or non-approved use of a drug or device for non-cancer indications or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. * (Part A only) Have received prior treatment with doxorubicin, daunorubicin, idarubicin, and/or other anthracyclines and anthracenediones * (Part A only) Have received prior radiation therapy to the mediastinal/pericardial area. * Have symptomatic central nervous system malignancy or metastasis. Participants with treated central nervous system (CNS) metastases are eligible for this study if they are not currently receiving corticosteroids and/or anticonvulsants, and their disease is asymptomatic and radiographically stable for at least 60 days. * Have an elective or a planned major surgery to be performed during the course of the study. * Have an uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure greater than class II of the New York Heart Association guideline, severe myocardial insufficiency, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Have unstable angina pectoris, angioplasty, cardiac stenting, or myocardial infarction 6 months prior to study entry. * Have a known allergy to any of the treatment components. * Have a history of allergic reactions attributed to compounds of chemical or biologic composition similar to that of olaratumab. * Have a known active fungal, bacterial, and/or known viral infection * Have a corrected QT interval of greater than 470 milliseconds (msec) on screening electrocardiogram (ECG) * Have a second primary malignancy that, in the judgment of the investigator and sponsor, may affect the interpretation of results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline to Study completion (Up To 3.5 Years) | 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. |
| Part A: Number of Participants With Dose Limiting Toxicities (DLTs) | Cycle 1 (21 Days) | 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. |
| Part B: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Olaratumab | 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 | Maximum observed serum concentration (Cmax) of olaratumab is reported. |
| Part B: Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of Olaratumab | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Olaratumab | 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 | Maximum observed serum concentration (Cmax) of olaratumab is reported. |
| Change From Baseline in Percentage of Participants With a Tumor Response | Baseline to Study completion (Up To 3.5 Years) | 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. |
| Part A: Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of Olaratumab | 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 | 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. |
| Part A: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Doxorubicin | 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 | Maximum observed plasma concentration (Cmax) of doxorubicin is reported. |
| Part A: Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of Doxorubicin | Cycle 1 Day 1 and Cycle 3 Day 1: Immediately postinfusion, 0.5, 1, 2, 4, 8, 24, 48, and 72 h postinfusion | Area under the concentration verses time curve from zero to infinity (AUC\[0-∞\]) of doxorubicin is reported. |
Countries
Japan
Participant flow
Pre-assignment details
Participants were considered to have competed the study if the study discontinued due to adverse event, progressive disease (PD) or withdrawal by subject.
Participants by arm
| Arm | Count |
|---|---|
| Part A Cohort 1: Olaratumab+Doxorubicin 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. | 7 |
| 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. | 6 |
| 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. | 6 |
| 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. | 6 |
| Total | 25 |
Baseline characteristics
| Characteristic | Part A Cohort 1: Olaratumab+Doxorubicin | Total | Part B: Olaratumab | Part A Cohort 3 Olaratumab + Doxorubicin | Part A Cohort 2: Olaratumab+Doxorubicin |
|---|---|---|---|---|---|
| Age, Continuous | 50.1 years STANDARD_DEVIATION 15.3 | 49.0 years STANDARD_DEVIATION 12.7 | 59.3 years STANDARD_DEVIATION 8.1 | 40.7 years STANDARD_DEVIATION 8.7 | 45.8 years STANDARD_DEVIATION 11 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants | 25 Participants | 6 Participants | 6 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Japan | 7 Participants | 25 Participants | 6 Participants | 6 Participants | 6 Participants |
| Sex: Female, Male Female | 4 Participants | 16 Participants | 5 Participants | 5 Participants | 2 Participants |
| Sex: Female, Male Male | 3 Participants | 9 Participants | 1 Participants | 1 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 7 / 7 | 6 / 6 | 6 / 6 | 5 / 6 |
| serious Total, serious adverse events | 1 / 7 | 4 / 6 | 1 / 6 | 2 / 6 |
Outcome results
Primary
Part A: Number of Participants With Dose Limiting Toxicities (DLTs)
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A Cohort 1: Olaratumab+Doxorubicin | Part A: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part A Cohort 2: Olaratumab+Doxorubicin | Part A: Number of Participants With Dose Limiting Toxicities (DLTs) | 1 Participants |
| Part A Cohort 3 Olaratumab + Doxorubicin | Part A: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
Primary
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
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A Cohort 1: Olaratumab+Doxorubicin | 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 |
| Part A Cohort 2: Olaratumab+Doxorubicin | 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 | 4 participants |
| Part A Cohort 3 Olaratumab + Doxorubicin | 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 |
Primary
Part B: Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of Olaratumab
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.
Time frame: 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 PK data in Part B.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A Cohort 1: Olaratumab+Doxorubicin | Part B: Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of Olaratumab | Cycle 1 Day 1: AUC(0-168h) | 23300 microgram*hour/mL (μg*h/mL) | Geometric Coefficient of Variation 26 |
| Part A Cohort 1: Olaratumab+Doxorubicin | Part B: Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of Olaratumab | Cycle 1 Day 8: AUC(0-336h) | 48100 microgram*hour/mL (μg*h/mL) | Geometric Coefficient of Variation 47 |
| Part A Cohort 1: Olaratumab+Doxorubicin | Part B: Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of Olaratumab | Cycle 3 Day 1: AUC(0-168h) | 39800 microgram*hour/mL (μg*h/mL) | Geometric Coefficient of Variation 14 |
| Part A Cohort 1: Olaratumab+Doxorubicin | Part B: Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of Olaratumab | Cycle 3 Day 8: AUC(0-336h) | NA microgram*hour/mL (μg*h/mL) | — |
Primary
Part B: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Olaratumab
Maximum observed serum concentration (Cmax) of olaratumab is reported.
Time frame: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A Cohort 1: Olaratumab+Doxorubicin | 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 A Cohort 1: Olaratumab+Doxorubicin | 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 A Cohort 1: Olaratumab+Doxorubicin | 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 A Cohort 1: Olaratumab+Doxorubicin | Part B: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Olaratumab | Cycle 3 Day 8 | 478 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 15 |
Secondary
Change From Baseline in Percentage of Participants With a Tumor Response
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A Cohort 1: Olaratumab+Doxorubicin | Change From Baseline in Percentage of Participants With a Tumor Response | 0 percentage of participants |
| Part A Cohort 2: Olaratumab+Doxorubicin | Change From Baseline in Percentage of Participants With a Tumor Response | 33.3 percentage of participants |
| Part A Cohort 3 Olaratumab + Doxorubicin | Change From Baseline in Percentage of Participants With a Tumor Response | 33.3 percentage of participants |
| Part B: Olaratumab | Change From Baseline in Percentage of Participants With a Tumor Response | 0 percentage of participants |
Secondary
Part A: Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of Doxorubicin
Area under the concentration verses time curve from zero to infinity (AUC\[0-∞\]) of doxorubicin is reported.
Time frame: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A Cohort 1: Olaratumab+Doxorubicin | Part A: Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of Doxorubicin | Cycle 1 Day 1 | 3070 nanogram*hour/mL (ng*h/mL) | Geometric Coefficient of Variation 12 |
| Part A Cohort 1: Olaratumab+Doxorubicin | Part A: Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of Doxorubicin | Cycle 3 Day 1 | NA nanogram*hour/mL (ng*h/mL) | — |
| Part A Cohort 2: Olaratumab+Doxorubicin | Part A: Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of Doxorubicin | Cycle 1 Day 1 | 3020 nanogram*hour/mL (ng*h/mL) | Geometric Coefficient of Variation 15 |
| Part A Cohort 2: Olaratumab+Doxorubicin | Part A: Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of Doxorubicin | Cycle 3 Day 1 | 3720 nanogram*hour/mL (ng*h/mL) | Geometric Coefficient of Variation 17 |
Secondary
Part A: Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of Olaratumab
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.
Time frame: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A Cohort 1: Olaratumab+Doxorubicin | Part A: Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of Olaratumab | Cycle 1 Day 1: AUC(0-168h) | 21700 microgram*hour per milliliter (μg*h/mL) | Geometric Coefficient of Variation 36 |
| Part A Cohort 1: Olaratumab+Doxorubicin | Part A: Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of Olaratumab | Cycle 1 Day 8: AUC(0-336h) | 47300 microgram*hour per milliliter (μg*h/mL) | Geometric Coefficient of Variation 32 |
| Part A Cohort 1: Olaratumab+Doxorubicin | Part A: Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of Olaratumab | Cycle 3 Day 1: AUC(0-168h) | 33600 microgram*hour per milliliter (μg*h/mL) | Geometric Coefficient of Variation 31 |
| Part A Cohort 1: Olaratumab+Doxorubicin | Part A: Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of Olaratumab | Cycle 3 Day 8: AUC(0-336h) | 63000 microgram*hour per milliliter (μg*h/mL) | Geometric Coefficient of Variation 28 |
| Part A Cohort 2: Olaratumab+Doxorubicin | Part A: Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of Olaratumab | Cycle 3 Day 8: AUC(0-336h) | 68400 microgram*hour per milliliter (μg*h/mL) | Geometric Coefficient of Variation 15 |
| Part A Cohort 2: Olaratumab+Doxorubicin | Part A: Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of Olaratumab | Cycle 1 Day 1: AUC(0-168h) | 21900 microgram*hour per milliliter (μg*h/mL) | Geometric Coefficient of Variation 25 |
| Part A Cohort 2: Olaratumab+Doxorubicin | Part A: Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of Olaratumab | Cycle 3 Day 1: AUC(0-168h) | 36000 microgram*hour per milliliter (μg*h/mL) | Geometric Coefficient of Variation 15 |
| Part A Cohort 2: Olaratumab+Doxorubicin | Part A: Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of Olaratumab | Cycle 1 Day 8: AUC(0-336h) | 42000 microgram*hour per milliliter (μg*h/mL) | Geometric Coefficient of Variation 36 |
| Part A Cohort 3 Olaratumab + Doxorubicin | Part A: Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of Olaratumab | Cycle 3 Day 8: AUC(0-336h) | 77700 microgram*hour per milliliter (μg*h/mL) | Geometric Coefficient of Variation 68 |
| Part A Cohort 3 Olaratumab + Doxorubicin | Part A: Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of Olaratumab | Cycle 1 Day 8: AUC(0-336h) | 74100 microgram*hour per milliliter (μg*h/mL) | Geometric Coefficient of Variation 42 |
| Part A Cohort 3 Olaratumab + Doxorubicin | Part A: Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of Olaratumab | Cycle 3 Day 1: AUC(0-168h) | 42500 microgram*hour per milliliter (μg*h/mL) | Geometric Coefficient of Variation 51 |
| Part A Cohort 3 Olaratumab + Doxorubicin | Part A: Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of Olaratumab | Cycle 1 Day 1: AUC(0-168h) | 34300 microgram*hour per milliliter (μg*h/mL) | Geometric Coefficient of Variation 29 |
Secondary
Part A: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Doxorubicin
Maximum observed plasma concentration (Cmax) of doxorubicin is reported.
Time frame: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A Cohort 1: Olaratumab+Doxorubicin | 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 Cohort 1: Olaratumab+Doxorubicin | Part A: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Doxorubicin | Cycle 3 Day 3 | 884 nanogram/milliliter (ng/mL | Geometric Coefficient of Variation 24 |
| Part A Cohort 1: Olaratumab+Doxorubicin | 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 Cohort 1: Olaratumab+Doxorubicin | 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 Cohort 1: Olaratumab+Doxorubicin | 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 Cohort 1: Olaratumab+Doxorubicin | Part A: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Doxorubicin | Cycle 3 Day 1 | 855 nanogram/milliliter (ng/mL | Geometric Coefficient of Variation 29 |
Secondary
Part A: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Doxorubicin
Maximum observed plasma concentration (Cmax) of doxorubicin is reported.
Time frame: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A Cohort 1: Olaratumab+Doxorubicin | Part A: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Doxorubicin | Cycle 1 Day 1 | 2660 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 25 |
| Part A Cohort 1: Olaratumab+Doxorubicin | Part A: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Doxorubicin | Cycle 3 Day 1 | NA nanogram/milliliter (ng/mL) | — |
| Part A Cohort 2: Olaratumab+Doxorubicin | Part A: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Doxorubicin | Cycle 3 Day 1 | 2900 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 19 |
| Part A Cohort 2: Olaratumab+Doxorubicin | Part A: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Doxorubicin | Cycle 1 Day 1 | 2790 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 12 |
Secondary
Part A: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Olaratumab
Maximum observed serum concentration (Cmax) of olaratumab is reported.
Time frame: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A Cohort 1: Olaratumab+Doxorubicin | Part A: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Olaratumab | Cycle 1 Day 1 | 274 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 30 |
| Part A Cohort 1: Olaratumab+Doxorubicin | Part A: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Olaratumab | Cycle 1 Day 8 | 353 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 40 |
| Part A Cohort 1: Olaratumab+Doxorubicin | Part A: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Olaratumab | Cycle 3 Day 1 | 351 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 28 |
| Part A Cohort 1: Olaratumab+Doxorubicin | Part A: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Olaratumab | Cycle 3 Day 8 | 415 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 28 |
| Part A Cohort 2: Olaratumab+Doxorubicin | Part A: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Olaratumab | Cycle 3 Day 8 | 474 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 13 |
| Part A Cohort 2: Olaratumab+Doxorubicin | Part A: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Olaratumab | Cycle 1 Day 1 | 301 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 25 |
| Part A Cohort 2: Olaratumab+Doxorubicin | Part A: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Olaratumab | Cycle 3 Day 1 | 390 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 13 |
| Part A Cohort 2: Olaratumab+Doxorubicin | Part A: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Olaratumab | Cycle 1 Day 8 | 351 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 20 |
| Part A Cohort 3 Olaratumab + Doxorubicin | Part A: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Olaratumab | Cycle 3 Day 8 | 541 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 41 |
| Part A Cohort 3 Olaratumab + Doxorubicin | Part A: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Olaratumab | Cycle 1 Day 8 | 610 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 33 |
| Part A Cohort 3 Olaratumab + Doxorubicin | Part A: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Olaratumab | Cycle 3 Day 1 | 545 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 34 |
| Part A Cohort 3 Olaratumab + Doxorubicin | Part A: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Olaratumab | Cycle 1 Day 1 | 470 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 27 |