Sarcoma, Soft Tissue
Conditions
Keywords
Sarcoma, Soft Tissue, Advanced Soft Tissue Sarcoma
Brief summary
The main purpose of this study is to gather information about the use of an investigational drug called olaratumab with a drug for soft tissue sarcoma called doxorubicin.
Interventions
BIOLOGICALOlaratumab
Olaratumab 15 mg/kg by intravenous transfusion (I.V.) on days 1+8 of a 21-day cycle
DRUGdoxorubicin
Doxorubicin 75 mg/m2 by intravenous injection on day 1 of the 21-day cycle.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* The participant has histologically- or cytologically-confirmed malignant soft tissue sarcoma * The participant has advanced soft tissue sarcoma (STS), not amenable to treatment with surgery or radiotherapy * The participant's Eastern Cooperative Oncology Group (ECOG) performance status is 0-2 * The participant has available tumor tissue from either the primary or metastatic tumor for determination of PDGFRα expression * The participant has adequate hematologic function as defined by an absolute neutrophil count (ANC) ≥ 1500 μL, hemoglobin ≥ 9.0 g/dL, and a platelet count of 100,000/μL obtained within 2 weeks prior to study entry * The participant has adequate hepatic function as defined by a total bilirubin ≤ 1.5 mg/dL, and aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 times the upper limit of normal (ULN) * The participant has adequate renal function as defined by serum creatinine ≤ 1.5 × the institutional ULN. If creatinine is above the ULN, the participant's creatinine clearance is ≥ 45 mL/min * Because the teratogenicity of Olaratumab is not known, women of childbearing potential (WOCBP) and sexually active males must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
Exclusion criteria
* The participant has histologically- or cytologically-confirmed Kaposi's sarcoma * The participant has untreated central nervous system metastases * The participant received prior treatment with doxorubicin, daunorubicin, idarubicin, and/or other anthracyclines and anthracenediones (ie, mitoxantrone) * The participant received prior radiation therapy to the mediastinal/pericardial area * The participant has a history of another primary cancer, with the exception of a) curatively resected nonmelanomatous skin cancer; b) curatively treated cervical carcinoma in situ; or c) other primary solid tumor treated with curative intent, no known active disease present, and no treatment administered during the last 3 years prior to study entry * The participant is receiving concurrent treatment with other anticancer therapy, including other chemotherapy, immunotherapy, hormonal therapy, radiotherapy, chemo-embolization, targeted therapy, or an investigational agent * The participant has an elective or a planned major surgery to be performed during the course of the study * The participant has an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, requiring parenteral antibiotics, symptomatic congestive heart failure, severe myocardial insufficiency, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * The participant has unstable angina pectoris, angioplasty, cardiac stenting, or myocardial infarction 6 months prior to study entry * The participant has known immunodeficiency virus (HIV) infection * The participant, if female, is pregnant or lactating * The participant has a known allergy to any of the treatment components
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | Randomization Until the First Radiographic Documentation of Objective Progression (Up to 29 Months) | PFS is measured from randomization until the first radiographic documentation of progression of disease (PD) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) or death from any cause. Participants who died without PD was considered to have progressed on the day of death. The following censoring rules applied: If no radiologic assessment at baseline or post baseline, participant was censored at the date of randomization. Participants were censored at the day of their last tumor assessment if no PD and were lost to follow up; If death or PD occurred after 2 or more consecutive missing radiographic visits, censoring occurred at the date of the last adequate radiographic visit. If participant started new treatment before PD, the participant was censored at the date of last tumor assessment prior to new therapy. If treatment was discontinued for reasons other than PD and no further assessment, censoring occurred at last tumor assessment. |
| Number of Participants With Treatment Related Adverse Events (TEAE), Adverse Events (AE) or Serious Adverse Events (SAE) for Safety for the Phase 1b Portion of the Study | Baseline Up to 30 Months | All Phase 1b participants who experienced at least 1 TEAE in the Phase 1b portion of the study. Adverse Event with missing relationship to study is counted as related. A summary of SAEs and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Objective Response (Objective Response Rate) | Randomization Until Progressive Disease (Up to 30 Months) | Objective Response Rate (ORR) is confirmed best overall tumor response of CR or PR. According to RECIST v1.1, PR defined as a \>30% decrease in the sum of the longest diameters (LD) of the target lesions, taking as reference the baseline sum of the LD; CR was defined as the disappearance of all target and non-target lesions. Percentage of participants was calculated as: total number of participants with a best tumor response of PR or CR among participants counted in the denominator/total number of participants treated with any amount of study drug, who has a complete radiographic assessment at baseline, and who has at least 1 complete radiographic assessment at postbaseline x 100%. |
| Percentage of Participants Who Are Progression-Free (PFS) at 3 Months | Randomization Until First Radiographic PD or Death from Any Cause (Up to 3 Months) | (PFS) rate is defined as the percentage of participants that are alive and progression-free 3 months after randomization. PFS is measured from randomization until the first radiographic progressive disease as defined by RECIST (version 1.1) or death from any cause. Participants who died without PD were considered to have progressed on the day of death. Censoring applied: If no radiologic assessment at baseline or post baseline, participant was censored at the date of randomization or the day of their last tumor assessment if no PD and were lost to follow up; If death or PD occurred after 2 or more consecutive missing radiographic visits, censoring occurred at the date of the last radiographic visit. If participant started new treatment before PD, participant was censored at the date of last tumor assessment prior to new therapy. If treatment was discontinued for reasons other than PD and no further assessment, censoring occurred at last tumor assessment. |
| Pharmacokinetic (PK) Maximum Concentration (Cmax) Cycle 1 Day 1, Cycle 3 Day 1 of Olaratumab | Cycle 1 Day 1: Preinfusion, End of Infusion,1hr,48hr,72hr,168 hr Post infusion; Cycle 3 Day 1:Preinfusion, End of Infusion,1hr,24hr,48hr,72hr,168hr Post Infusion | — |
| Number of Participants With AEs and SAEs for Phase 2 Portion | Baseline, Up to 30 Months | A summary of SAEs and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module. |
| PK: Area Under Concentration Curve Versus Time (AUCτ) Cycle 1 Day 8, Cycle 3 Day 8 of Olaratumab | Cycle 1 Day 8:Preinfusion,1hr,72hr,168hr Post Infusion; Cycle 3 Day 8: Preinfusion,1hr,24hr,72hr,168hr Post Infusion | AUCτ = area under the concentration versus time curve during one dosing interval with a measurable concentration. |
| PK: Half-Life (T1/2) Cycle 1 Day 8, Cycle 3 Day 8 of Olaratumab | Cycle 1 Day 8:Preinfusion,1hr,72hr,168hr Post Infusion; Cycle 3 Day 8: Preinfusion,1hr,24hr,72hr,168hr Post Infusion | — |
| Percentage of Participants With Anti-Olaratumab Antibody Assessment | Baseline, Up to 30 Months | Participants with Treatment Emergent (TE) anti-olaratumab antibodies were participants with a 4-fold increase (2 dilutions) increase over a positive baseline antibody titer or for a negative baseline titer, a participant with an increase from the baseline to a level of 1:20. |
| PK: Minimum Concentration (Cmin) Cycle 1 Day 8, Cycle 3 Day 8 of Olaratumab | Cycle 1 Day 8: Preinfusion, 1hr,72hr,168hr Post Infusion; Cycle 3 Day 8: Preinfusion,1hr, 24hr,72hr,168hr Post Infusion | — |
| Overall Survival (OS) | Randomization to the Date of Death From Any Cause (Up To 47 Months) | OS was defined as the date of randomization to the date of death from any cause. Reasons for censoring OS were that participant was known to be alive, participant was lost to follow up during the study or participant withdrew consent to follow up. |
Countries
United States
Participant flow
Pre-assignment details
Participants who had evidence of progressive disease (PD), died, or received optional olaratumab treatment on the doxorubicin (dox) monotherapy arm were considered to have completed the study. This includes participants who discontinued treatment due to non-PD reasons, but had PD at End of Study.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1b: Olaratumab + Doxorubicin All cycles are 21 days.
Cycles 1-8: Olaratumab 15 milligram/kilogram (mg/kg) on days 1+8, and doxorubicin 75 milligram/square meter (mg/m2) on day 1
All subsequent cycles until progression:
Olaratumab 15 mg/kg by intravenous IV on days 1+8 of a 21-day cycle | 15 |
| Phase 2: Olaratumab + Doxorubicin All cycles are 21 days.
Cycles 1-8: Olaratumab 15 mg/kg on days 1+8, and doxorubicin 75 mg/m2 on day 1
All subsequent cycles until progression:
Olaratumab 15 mg/kg by IV on days 1+8 of a 21-day cycle | 66 |
| Phase 2: Doxorubicin All cycles are 21 days.
Cycles 1-8: doxorubicin 75 mg/m2 on day 1
At disease progression: optional Olaratumab 15 mg/kg on days 1+8 until further progression. | 67 |
| Total | 148 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Optional Olaratumab Monotherapy on Dox | Adverse Event | 0 | 0 | 0 | 1 |
| Optional Olaratumab Monotherapy on Dox | On Study Treatment | 0 | 0 | 0 | 2 |
| Optional Olaratumab Monotherapy on Dox | Withdrawal by Subject | 0 | 0 | 0 | 2 |
| Phase 1b and Phase 2 | Adverse Event | 1 | 0 | 2 | 0 |
| Phase 1b and Phase 2 | Off Treatment but alive and on study | 0 | 1 | 1 | 0 |
| Phase 1b and Phase 2 | Other Therapy Started | 0 | 3 | 3 | 0 |
| Phase 1b and Phase 2 | Participant was beyond maximum weight | 0 | 0 | 1 | 0 |
| Phase 1b and Phase 2 | Withdrawal by Subject | 1 | 6 | 2 | 0 |
Baseline characteristics
| Characteristic | Total | Phase 1b: Olaratumab + Doxorubicin | Phase 2: Olaratumab + Doxorubicin | Phase 2: Doxorubicin |
|---|---|---|---|---|
| Age, Continuous | 56.7 years STANDARD_DEVIATION 10.62 | 48.7 years STANDARD_DEVIATION 13.16 | 56.8 years STANDARD_DEVIATION 12.53 | 55.3 years STANDARD_DEVIATION 12.96 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 1 Participants | 6 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 138 Participants | 14 Participants | 60 Participants | 64 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 2 Participants | 6 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 1 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 127 Participants | 12 Participants | 55 Participants | 60 Participants |
| Region of Enrollment United States | 148 participants | 15 participants | 66 participants | 67 participants |
| Sex: Female, Male Female | 82 Participants | 8 Participants | 40 Participants | 34 Participants |
| Sex: Female, Male Male | 66 Participants | 7 Participants | 26 Participants | 33 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 | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 14 / 15 | 63 / 64 | 64 / 65 | 24 / 30 |
| serious Total, serious adverse events | 7 / 15 | 27 / 64 | 26 / 65 | 9 / 30 |
Outcome results
Primary
Number of Participants With Treatment Related Adverse Events (TEAE), Adverse Events (AE) or Serious Adverse Events (SAE) for Safety for the Phase 1b Portion of the Study
All Phase 1b participants who experienced at least 1 TEAE in the Phase 1b portion of the study. Adverse Event with missing relationship to study is counted as related. A summary of SAEs and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module.
Time frame: Baseline Up to 30 Months
Population: All participants in Phase 1b.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 2: Olaratumab + Doxorubicin | Number of Participants With Treatment Related Adverse Events (TEAE), Adverse Events (AE) or Serious Adverse Events (SAE) for Safety for the Phase 1b Portion of the Study | Any AE | 14 participants |
| Phase 2: Olaratumab + Doxorubicin | Number of Participants With Treatment Related Adverse Events (TEAE), Adverse Events (AE) or Serious Adverse Events (SAE) for Safety for the Phase 1b Portion of the Study | Any SAE | 7 participants |
Primary
Progression-free Survival (PFS)
PFS is measured from randomization until the first radiographic documentation of progression of disease (PD) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) or death from any cause. Participants who died without PD was considered to have progressed on the day of death. The following censoring rules applied: If no radiologic assessment at baseline or post baseline, participant was censored at the date of randomization. Participants were censored at the day of their last tumor assessment if no PD and were lost to follow up; If death or PD occurred after 2 or more consecutive missing radiographic visits, censoring occurred at the date of the last adequate radiographic visit. If participant started new treatment before PD, the participant was censored at the date of last tumor assessment prior to new therapy. If treatment was discontinued for reasons other than PD and no further assessment, censoring occurred at last tumor assessment.
Time frame: Randomization Until the First Radiographic Documentation of Objective Progression (Up to 29 Months)
Population: All randomized participants in Phase 2. Per protocol, phase 1b and optional Olaratumab monotherapy data was exploratory and not collected for this outcome measure. Censored Participants = Phase 2 Olaratumab + Doxorubicin = 11 and Doxorubicin = 19.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 2: Olaratumab + Doxorubicin | Progression-free Survival (PFS) | 6.6 Month |
| Phase 2: Doxorubicin | Progression-free Survival (PFS) | 4.1 Month |
p-value: 0.061595% CI: [0.442, 1.021]Log Rank
Secondary
Number of Participants With AEs and SAEs for Phase 2 Portion
A summary of SAEs and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module.
Time frame: Baseline, Up to 30 Months
Population: All randomized participants who received at least 1 dose of study drug in Phase 2 and optional Olaratumab monotherapy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 2: Olaratumab + Doxorubicin | Number of Participants With AEs and SAEs for Phase 2 Portion | Any AE | 63 participants |
| Phase 2: Olaratumab + Doxorubicin | Number of Participants With AEs and SAEs for Phase 2 Portion | Any SAE | 27 participants |
| Phase 2: Doxorubicin | Number of Participants With AEs and SAEs for Phase 2 Portion | Any AE | 64 participants |
| Phase 2: Doxorubicin | Number of Participants With AEs and SAEs for Phase 2 Portion | Any SAE | 26 participants |
| Phase 2: Doxorubicin: Optional Olaratumab After Progression | Number of Participants With AEs and SAEs for Phase 2 Portion | Any AE | 24 participants |
| Phase 2: Doxorubicin: Optional Olaratumab After Progression | Number of Participants With AEs and SAEs for Phase 2 Portion | Any SAE | 9 participants |
Secondary
Overall Survival (OS)
OS was defined as the date of randomization to the date of death from any cause. Reasons for censoring OS were that participant was known to be alive, participant was lost to follow up during the study or participant withdrew consent to follow up.
Time frame: Randomization to the Date of Death From Any Cause (Up To 47 Months)
Population: All randomized participants in Phase 2. Per protocol, phase 1b and optional Olaratumab monotherapy data was exploratory and not collected for this outcome measure. Censored participants = Phase 2 Olaratumab + Doxorubicin = 27 and Doxorubicin = 15.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 2: Olaratumab + Doxorubicin | Overall Survival (OS) | 26.5 Months |
| Phase 2: Doxorubicin | Overall Survival (OS) | 14.7 Months |
p-value: 0.000395% CI: [0.301, 0.71]Log Rank
Secondary
Percentage of Participants Who Are Progression-Free (PFS) at 3 Months
(PFS) rate is defined as the percentage of participants that are alive and progression-free 3 months after randomization. PFS is measured from randomization until the first radiographic progressive disease as defined by RECIST (version 1.1) or death from any cause. Participants who died without PD were considered to have progressed on the day of death. Censoring applied: If no radiologic assessment at baseline or post baseline, participant was censored at the date of randomization or the day of their last tumor assessment if no PD and were lost to follow up; If death or PD occurred after 2 or more consecutive missing radiographic visits, censoring occurred at the date of the last radiographic visit. If participant started new treatment before PD, participant was censored at the date of last tumor assessment prior to new therapy. If treatment was discontinued for reasons other than PD and no further assessment, censoring occurred at last tumor assessment.
Time frame: Randomization Until First Radiographic PD or Death from Any Cause (Up to 3 Months)
Population: All randomized participants in Phase 2. Per protocol, phase 1b and optional Olaratumab monotherapy data was exploratory and not collected for this outcome measure. Censored Participants = Phase 2 Olaratumab + Doxorubicin = 11 and Doxorubicin = 19.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 2: Olaratumab + Doxorubicin | Percentage of Participants Who Are Progression-Free (PFS) at 3 Months | 69.0 percentage of participants |
| Phase 2: Doxorubicin | Percentage of Participants Who Are Progression-Free (PFS) at 3 Months | 59.9 percentage of participants |
Secondary
Percentage of Participants With Anti-Olaratumab Antibody Assessment
Participants with Treatment Emergent (TE) anti-olaratumab antibodies were participants with a 4-fold increase (2 dilutions) increase over a positive baseline antibody titer or for a negative baseline titer, a participant with an increase from the baseline to a level of 1:20.
Time frame: Baseline, Up to 30 Months
Population: All participants who had baseline and post baseline anti-olaratumab antibodies.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 2: Olaratumab + Doxorubicin | Percentage of Participants With Anti-Olaratumab Antibody Assessment | 9.1 percentage of participants |
| Phase 2: Doxorubicin | Percentage of Participants With Anti-Olaratumab Antibody Assessment | 5.2 percentage of participants |
| Phase 2: Doxorubicin: Optional Olaratumab After Progression | Percentage of Participants With Anti-Olaratumab Antibody Assessment | 6.3 percentage of participants |
Secondary
Percentage of Participants With Objective Response (Objective Response Rate)
Objective Response Rate (ORR) is confirmed best overall tumor response of CR or PR. According to RECIST v1.1, PR defined as a \>30% decrease in the sum of the longest diameters (LD) of the target lesions, taking as reference the baseline sum of the LD; CR was defined as the disappearance of all target and non-target lesions. Percentage of participants was calculated as: total number of participants with a best tumor response of PR or CR among participants counted in the denominator/total number of participants treated with any amount of study drug, who has a complete radiographic assessment at baseline, and who has at least 1 complete radiographic assessment at postbaseline x 100%.
Time frame: Randomization Until Progressive Disease (Up to 30 Months)
Population: All randomized participants in Phase 2 and optional Olaratumab monotherapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 2: Olaratumab + Doxorubicin | Percentage of Participants With Objective Response (Objective Response Rate) | 18.2 percentage of participants |
| Phase 2: Doxorubicin | Percentage of Participants With Objective Response (Objective Response Rate) | 11.9 percentage of participants |
| Phase 2: Doxorubicin: Optional Olaratumab After Progression | Percentage of Participants With Objective Response (Objective Response Rate) | 0 percentage of participants |
Secondary
Pharmacokinetic (PK) Maximum Concentration (Cmax) Cycle 1 Day 1, Cycle 3 Day 1 of Olaratumab
Time frame: Cycle 1 Day 1: Preinfusion, End of Infusion,1hr,48hr,72hr,168 hr Post infusion; Cycle 3 Day 1:Preinfusion, End of Infusion,1hr,24hr,48hr,72hr,168hr Post Infusion
Population: All participants who had evaluable PK data in Phase 1b and Phase 2. Per protocol, optional Olaratumab monotherapy data was exploratory and not collected for this outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 2: Olaratumab + Doxorubicin | Pharmacokinetic (PK) Maximum Concentration (Cmax) Cycle 1 Day 1, Cycle 3 Day 1 of Olaratumab | Cycle 1 Day 1 (n=60) | 284 nanogram/milliliter (μg/mL ) | Geometric Coefficient of Variation 23.3 |
| Phase 2: Olaratumab + Doxorubicin | Pharmacokinetic (PK) Maximum Concentration (Cmax) Cycle 1 Day 1, Cycle 3 Day 1 of Olaratumab | Cycle 3 Day 1 (n=30) | 404 nanogram/milliliter (μg/mL ) | Geometric Coefficient of Variation 31.6 |
Secondary
PK: Area Under Concentration Curve Versus Time (AUCτ) Cycle 1 Day 8, Cycle 3 Day 8 of Olaratumab
AUCτ = area under the concentration versus time curve during one dosing interval with a measurable concentration.
Time frame: Cycle 1 Day 8:Preinfusion,1hr,72hr,168hr Post Infusion; Cycle 3 Day 8: Preinfusion,1hr,24hr,72hr,168hr Post Infusion
Population: All participants who had evaluable PK data in Phase1b and Phase 2. Per protocol, optional Olaratumab monotherapy data was exploratory and not collected for this outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 2: Olaratumab + Doxorubicin | PK: Area Under Concentration Curve Versus Time (AUCτ) Cycle 1 Day 8, Cycle 3 Day 8 of Olaratumab | Cycle 1 Day 8 (n=7) | 39200 microgram•hour/milliliter (μg•h/mL) | Geometric Coefficient of Variation 29 |
| Phase 2: Olaratumab + Doxorubicin | PK: Area Under Concentration Curve Versus Time (AUCτ) Cycle 1 Day 8, Cycle 3 Day 8 of Olaratumab | Cycle 3 Day 8 (n=4) | 47300 microgram•hour/milliliter (μg•h/mL) | Geometric Coefficient of Variation 35 |
Secondary
PK: Half-Life (T1/2) Cycle 1 Day 8, Cycle 3 Day 8 of Olaratumab
Time frame: Cycle 1 Day 8:Preinfusion,1hr,72hr,168hr Post Infusion; Cycle 3 Day 8: Preinfusion,1hr,24hr,72hr,168hr Post Infusion
Population: All participants who had evaluable PK data in Phase 1b and Phase 2. Per protocol, optional Olaratumab monotherapy data was exploratory and not collected for this outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Phase 2: Olaratumab + Doxorubicin | PK: Half-Life (T1/2) Cycle 1 Day 8, Cycle 3 Day 8 of Olaratumab | Cycle 1 Day 8 (n=7) | 6.70 Days |
| Phase 2: Olaratumab + Doxorubicin | PK: Half-Life (T1/2) Cycle 1 Day 8, Cycle 3 Day 8 of Olaratumab | Cycle 3 Day 8 (n=2) | 9.80 Days |
Secondary
PK: Minimum Concentration (Cmin) Cycle 1 Day 8, Cycle 3 Day 8 of Olaratumab
Time frame: Cycle 1 Day 8: Preinfusion, 1hr,72hr,168hr Post Infusion; Cycle 3 Day 8: Preinfusion,1hr, 24hr,72hr,168hr Post Infusion
Population: All participants who had evaluable PK data in Phase 1b and Phase 2. Per protocol, optional Olaratumab monotherapy data was exploratory and not collected for this outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 2: Olaratumab + Doxorubicin | PK: Minimum Concentration (Cmin) Cycle 1 Day 8, Cycle 3 Day 8 of Olaratumab | Cycle 1 Day 8 (n=52) | 66.5 μg/mL | Geometric Coefficient of Variation 40.4 |
| Phase 2: Olaratumab + Doxorubicin | PK: Minimum Concentration (Cmin) Cycle 1 Day 8, Cycle 3 Day 8 of Olaratumab | Cycle 3 Day 8 (n=29) | 123 μg/mL | Geometric Coefficient of Variation 39.6 |