Neoplasm Metastasis
Conditions
Brief summary
The main purpose of this study is to evaluate the safety of different doses of olaratumab and to determine which dose should be used for future pediatric studies. The present study is open to children with advanced cancer or cancer that has spread to another part of the body. The study has three parts. In the first two parts, a specific dose of olaratumab will be given in 21 day cycles, followed by one of three standard chemotherapy regimens. In the third part, a specific dose of olaratumab will be given with one of three standard chemotherapy regimens in 21 day cycles. Participants will only enroll in one part.
Interventions
DRUGOlaratumab
Olaratumab administered IV.
DRUGDoxorubicin
Doxorubicin administered IV.
DRUGVincristine
Vincristine administered IV.
DRUGIrinotecan
Irinotecan administered IV.
DRUGIfosfamide
Ifosfamide administered IV.
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 17 Years
Healthy volunteers
No
Inclusion criteria
* The participant must have histological or cytological evidence of a diagnosis of solid tumor, excluding lymphomas and melanoma, but including central nervous system (CNS) tumors, that is relapsed or refractory, not be amenable to curative treatment. * The participant has the presence of measurable and/or nonmeasurable but evaluable disease as defined by the Response Evaluation Criteria In Solid Tumors (RECIST Version 1.1). Response Assessment in Neuro-Oncology (RANO) Criteria or Macdonald Criteria should be used for CNS tumors. * The participant has a Lansky (\<16 years of age) or Karnofsky (≥16 years of age) performance score of at least 50. * The participant has adequate hematologic, organ, and coagulation function ≤2 weeks (14 days) prior to first dose of study drug: * Absolute neutrophil count (ANC) ≥750 cubic millimeters (mm³) * Platelets ≥75,000/mm³ * Hemoglobin ≥8 grams per deciliter (g/dL) * Total bilirubin (sum of conjugated + unconjugated) ≤1.5 x upper limit of normal (ULN) for age * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0 x ULN * Serum creatinine is based on age/gender * Adequate coagulation function as defined by International Normalized Ratio ≤1.5 or prothrombin time ≤1.5 x ULN, and partial thromboplastin time ≤1.5 x ULN * Both female and male participants of child-bearing potential must agree to use highly effective contraceptive precautions during the trial and up to 3 months following the last dose of olaratumab, or longer for other study drugs according to their label. * Participants must have fully recovered from the acute toxic effects of all prior anticancer therapies or must adhere to post-treatment conditions as follows: * Myelosuppressive chemotherapy * Hematopoietic growth factors * Biologic (anti-neoplastic agent) * Antibody therapy * Radiation * Stem cell infusion without traumatic brain injury * Corticosteroids
Exclusion criteria
* Have received treatment within 21 days of the initial dose of olaratumab with an investigational product or non-approved use of a drug or device or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. * Participants that have had bone marrow or solid organ transplant are excluded. * The participant has an active fungal, bacterial, and/or known severe viral infection including human immunodeficiency virus (HIV) or viral (A, B, or C) hepatitis (screening is not required). * Female participants who are pregnant or breastfeeding are excluded. * If the participant is to be enrolled in the doxorubicin combination arm, a left ventricular dysfunction (LVEF \< 50%) or shortening fraction of \<27% by echocardiogram (either multigated acquisition \[MUGA\] or echocardiogram \[ECHO\] are required, not both). * Participants that have received prior anthracycline therapy if the participant is to be enrolled in the doxorubicin combination arm.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Olaratumab Dose Limiting Toxicities (DLTs) | Parts A and B: Cycle 1 through Cycle 2 in each arm (21-day cycle); Part C: Cycle 1 only (21-day cycle) | A dose limiting toxicity (DLT) was defined as an adverse event (AE) during the first 21 days that was possibly related to the study drug and fulfilled any of the following criteria using the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0: CTCAE Grade 3 nonhematologic toxicity, grade 4 neutropenia that lasted longer than 2 weeks, grade ≥3 thrombocytopenia complicated by hemorrhage, and any hematologic toxicity that caused a cycle delay of \>14 days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK: Maximum Concentration (Cmax) of Olaratumab Part B | Cycle 1, Day 8 and Cycle 2, Days 1 and 8: 1.25 hour (h), 2.5 h, 3.5h Postdose | PK: Maximum serum concentration (Cmax) data of Olaratumab was reported from available sample data. |
| PK: Maximum Concentration (Cmax) of Olaratumab Part C | Cycle 1, Days 1 and 8; Cycle 2, Days 1 and 8: 1.25 hour (h), 2.5 h, 3.5h Postdose | Pharmacokinetics (PK): Maximum serum concentration (Cmax) data of Olaratumab was reported from available sample data. |
| PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part A | Cycles 1, 2, 3-25; Day 8: 336 Hours Postdose | PK: Trough serum concentration (Cmin) of Olaratumab was reported. A sample was collected every other cycle from cycles 1, 2, 3-25. |
| PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part B | Cycles 1, 2, 3-25; Day 8: 336 Hours Postdose | PK: Trough serum concentration (Cmin) of Olaratumab was reported. A sample was collected every other cycle from cycles 1, 2, 3-25. |
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of Olaratumab Part A | Cycle 1, Day 8 and Cycle 2, Days 1 and 8: 1.25 hour (h), 2.5 h, 3.5h Postdose | Pharmacokinetics (PK): Maximum serum concentration (Cmax) data of Olaratumab was reported from available sample data. |
| Percentage of Participants With a Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR]) | Baseline to objective progression or start of new anti-cancer therapy (Up to 7 months) | Objective Response Rate (ORR) is the percentage of participants achieving a 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. |
| Progression Free Survival (PFS) | Baseline to radiological disease progression or death from any cause (Up to 2 Years) | Progression-free survival (PFS) is defined as the time from baseline to the first date of radiological disease progression or death due to any cause. Progressive disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). The appearance of one or more new lesions is also considered progression. 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. |
| Percentage of Participants With Treatment Emergent (TE) Positive Anti-Olaratumab Antibodies | From Baseline to Study Completion (Up to 33 Months) | Percentage of participants with a TE positive anti-olaratumab antibodies defined as a participant with a 4-fold (2 dilutions) increase over a positive baseline antibody titer. |
| PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part C | Cycles 1, 2, 3-25; Day 8: 336 Hours Postdose | PK: Trough serum concentration (Cmin) of Olaratumab was reported. A sample was collected every other cycle from cycles 1, 2, 3-25. |
Countries
Japan, United States
Participant flow
Pre-assignment details
Completers include the participants who died due to any cause or disease progression, alive and on study at conclusion, but off treatment.
Participants by arm
| Arm | Count |
|---|---|
| Olaratumab + Vincristine + Irinotecan (Part A) Cycle 1: Olaratumab 15 milligram/kilogram (mg/kg) was administered alone intravenously (IV) on Days 1 and 8.
Cycle 2 and beyond: Olaratumab 15 mg/kg and vincristine administered IV on Days 1 and 8. Irinotecan administered IV on Days 1 through 5. Treatment will cease when discontinuation criterion is met.
All cycles are 21 days. | 10 |
| Olaratumab + Doxorubicin (Part A) Cycle 1: Olaratumab 15 mg/kg was administered alone IV on Days 1 and 8.
Cycle 2 and beyond: Olaratumab 15 mg/kg administered IV on Days 1 and 8 and doxorubicin administered IV on Days 1 and 2. Treatment will cease when discontinuation criterion is met.
All cycles are 21 days. | 11 |
| Olaratumab + Ifosfamide (Part A) Cycle 1: Olaratumab 15 mg/kg was administered alone IV on Days 1 and 8.
Cycle 2 and beyond: Olaratumab 15mg/kg administered IV on Days 1 and 8 of each cycle. Ifosfamide administered IV on Days 1 through 5. Treatment will cease when discontinuation criterion is met.
All cycles are 21 days. | 9 |
| Olaratumab + Vincristine + Irinotecan (Part B) Cycle 1: Olaratumab 20 mg/kg was administered alone IV on Days 1 and 8.
Cycle 2 and beyond: Olaratumab 20 mg/kg and vincristine administered IV on Days 1 and 8. Irinotecan administered IV on Days 1 through 5. Treatment will cease when discontinuation criterion is met.
All cycles are 21 days. | 10 |
| Olaratumab + Doxorubicin (Part B) Cycle 1: Olaratumab 20 mg/kg was administered alone IV on Days 1 and 8.
Cycle 2 and beyond: Olaratumab 20 mg/kg administered IV on Days 1 and 8 and doxorubicin administered IV on Days 1 and 2. Treatment will cease when discontinuation criterion is met.
All cycles are 21 days. | 1 |
| Olaratumab + Ifosfamide (Part B) Cycle1: Olaratumab 20 mg/kg was administered alone IV on Days 1 and 8.
Cycle 2 and beyond: Olaratumab 20 mg/kg administered IV on Days 1 and 8 of each cycle. Ifosfamide administered IV on Days 1 through 5. Treatment will cease when discontinuation criterion is met.
All cycles are 21 days. | 13 |
| Olaratumab + Vincristine + Irinotecan (Part C) Cycle 1 and beyond: Olaratumab 20 mg/kg and vincristine administered IV on Days 1 and 8. Irinotecan administered IV on Days 1 through 5. Treatment will cease when discontinuation criterion is met.
All cycles are 21 days. | 6 |
| Olaratumab + Ifosfamide (Part C) Cycle 1 and beyond: Olaratumab 20 mg/kg administered IV on Days 1 and 8 of each cycle. Ifosfamide administered IV on Days 1 though 5. Treatment will cease when discontinuation criterion is met.
All cycles are 21 days. | 4 |
| Olaratumab + Doxorubicin (Part C) Cycle 1 and beyond: Olaratumab 20 mg/kg administered IV on Days 1 and 8 and doxorubicin administered IV on Days 1 and 2. Treatment will cease when discontinuation criterion is met.
All cycles are 21 days. | 4 |
| Total | 68 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 2 | 3 | 2 | 1 | 3 | 1 | 1 | 2 |
| Overall Study | Withdrawal by parent or guardian | 2 | 1 | 0 | 1 | 0 | 0 | 2 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Olaratumab + Vincristine + Irinotecan (Part A) | Total | Olaratumab + Doxorubicin (Part C) | Olaratumab + Ifosfamide (Part C) | Olaratumab + Vincristine + Irinotecan (Part C) | Olaratumab + Ifosfamide (Part B) | Olaratumab + Doxorubicin (Part B) | Olaratumab + Vincristine + Irinotecan (Part B) | Olaratumab + Ifosfamide (Part A) | Olaratumab + Doxorubicin (Part A) |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 9.9 years STANDARD_DEVIATION 5.5 | 10.0 years STANDARD_DEVIATION 4.8 | 10.8 years STANDARD_DEVIATION 5.1 | 8.0 years STANDARD_DEVIATION 7 | 9.7 years STANDARD_DEVIATION 5.4 | 12.5 years STANDARD_DEVIATION 3.8 | NA years | 10.6 years STANDARD_DEVIATION 4.9 | 10.7 years STANDARD_DEVIATION 4.3 | 6.8 years STANDARD_DEVIATION 4.3 |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants | 14 Participants | 1 Participants | 1 Participants | 2 Participants | 3 Participants | 0 Participants | 1 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Missing | 0 Participants | 7 Participants | 1 Participants | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 9 Participants | 43 Participants | 0 Participants | 0 Participants | 1 Participants | 10 Participants | 1 Participants | 8 Participants | 7 Participants | 7 Participants |
| Race/Ethnicity, Customized Not Reported | 0 Participants | 4 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 11 Participants | 3 Participants | 3 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 8 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 9 Participants | 46 Participants | 1 Participants | 1 Participants | 3 Participants | 11 Participants | 1 Participants | 7 Participants | 5 Participants | 8 Participants |
| Region of Enrollment Japan | 0 Participants | 9 Participants | 3 Participants | 3 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 10 Participants | 59 Participants | 1 Participants | 1 Participants | 3 Participants | 13 Participants | 1 Participants | 10 Participants | 9 Participants | 11 Participants |
| Sex: Female, Male Female | 4 Participants | 28 Participants | 2 Participants | 1 Participants | 4 Participants | 6 Participants | 0 Participants | 6 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 6 Participants | 40 Participants | 2 Participants | 3 Participants | 2 Participants | 7 Participants | 1 Participants | 4 Participants | 7 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 10 | 1 / 9 | 2 / 11 | 2 / 10 | 2 / 13 | 0 / 1 | 0 / 6 | 0 / 4 | 0 / 4 |
| other Total, other adverse events | 10 / 10 | 9 / 9 | 11 / 11 | 9 / 10 | 13 / 13 | 1 / 1 | 6 / 6 | 4 / 4 | 4 / 4 |
| serious Total, serious adverse events | 3 / 10 | 4 / 9 | 2 / 11 | 5 / 10 | 7 / 13 | 0 / 1 | 2 / 6 | 1 / 4 | 4 / 4 |
Outcome results
Primary
Number of Participants With Olaratumab Dose Limiting Toxicities (DLTs)
A dose limiting toxicity (DLT) was defined as an adverse event (AE) during the first 21 days that was possibly related to the study drug and fulfilled any of the following criteria using the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0: CTCAE Grade 3 nonhematologic toxicity, grade 4 neutropenia that lasted longer than 2 weeks, grade ≥3 thrombocytopenia complicated by hemorrhage, and any hematologic toxicity that caused a cycle delay of \>14 days.
Time frame: Parts A and B: Cycle 1 through Cycle 2 in each arm (21-day cycle); Part C: Cycle 1 only (21-day cycle)
Population: All participants who received at least one dose of study drug and had DLTs.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Olaratumab + Vincristine + Irinotecan (Part A) | Number of Participants With Olaratumab Dose Limiting Toxicities (DLTs) | 0 Participants |
| Olaratumab + Ifosfamide (Part A) | Number of Participants With Olaratumab Dose Limiting Toxicities (DLTs) | 1 Participants |
| Olaratumab + Doxorubicin (Part A) | Number of Participants With Olaratumab Dose Limiting Toxicities (DLTs) | 0 Participants |
| Olaratumab + Vincristine + Irinotecan (Part B) | Number of Participants With Olaratumab Dose Limiting Toxicities (DLTs) | 1 Participants |
| Olaratumab + Ifosfamide (Part B) | Number of Participants With Olaratumab Dose Limiting Toxicities (DLTs) | 0 Participants |
| Olaratumab + Doxorubicin (Part B) | Number of Participants With Olaratumab Dose Limiting Toxicities (DLTs) | 1 Participants |
| Olaratumab + Vincristine + Irinotecan (Part C) | Number of Participants With Olaratumab Dose Limiting Toxicities (DLTs) | 1 Participants |
| Olaratumab + Ifosfamide (Part C) | Number of Participants With Olaratumab Dose Limiting Toxicities (DLTs) | 0 Participants |
| Olaratumab + Doxorubicin (Part C) | Number of Participants With Olaratumab Dose Limiting Toxicities (DLTs) | 0 Participants |
Secondary
Percentage of Participants With a Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])
Objective Response Rate (ORR) is the percentage of participants achieving a 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.
Time frame: Baseline to objective progression or start of new anti-cancer therapy (Up to 7 months)
Population: All participants who received at least one dose of study drug and had evaluable ORR data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olaratumab + Vincristine + Irinotecan (Part A) | Percentage of Participants With a Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR]) | 0 percentage of participants |
| Olaratumab + Ifosfamide (Part A) | Percentage of Participants With a Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR]) | 0 percentage of participants |
| Olaratumab + Doxorubicin (Part A) | Percentage of Participants With a Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR]) | 9.1 percentage of participants |
| Olaratumab + Vincristine + Irinotecan (Part B) | Percentage of Participants With a Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR]) | 20.0 percentage of participants |
| Olaratumab + Ifosfamide (Part B) | Percentage of Participants With a Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR]) | 0 percentage of participants |
| Olaratumab + Doxorubicin (Part B) | Percentage of Participants With a Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR]) | 0 percentage of participants |
| Olaratumab + Vincristine + Irinotecan (Part C) | Percentage of Participants With a Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR]) | 0 percentage of participants |
| Olaratumab + Ifosfamide (Part C) | Percentage of Participants With a Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR]) | 0 percentage of participants |
| Olaratumab + Doxorubicin (Part C) | Percentage of Participants With a Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR]) | 25.0 percentage of participants |
Secondary
Percentage of Participants With Treatment Emergent (TE) Positive Anti-Olaratumab Antibodies
Percentage of participants with a TE positive anti-olaratumab antibodies defined as a participant with a 4-fold (2 dilutions) increase over a positive baseline antibody titer.
Time frame: From Baseline to Study Completion (Up to 33 Months)
Population: All participants who received at least one dose of study drug and had evaluable baseline sample and at least 1 evaluable post baseline sample.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olaratumab + Vincristine + Irinotecan (Part A) | Percentage of Participants With Treatment Emergent (TE) Positive Anti-Olaratumab Antibodies | 0 percentage of participants |
| Olaratumab + Ifosfamide (Part A) | Percentage of Participants With Treatment Emergent (TE) Positive Anti-Olaratumab Antibodies | 0 percentage of participants |
| Olaratumab + Doxorubicin (Part A) | Percentage of Participants With Treatment Emergent (TE) Positive Anti-Olaratumab Antibodies | 0 percentage of participants |
| Olaratumab + Vincristine + Irinotecan (Part B) | Percentage of Participants With Treatment Emergent (TE) Positive Anti-Olaratumab Antibodies | 0 percentage of participants |
| Olaratumab + Ifosfamide (Part B) | Percentage of Participants With Treatment Emergent (TE) Positive Anti-Olaratumab Antibodies | 0 percentage of participants |
| Olaratumab + Doxorubicin (Part B) | Percentage of Participants With Treatment Emergent (TE) Positive Anti-Olaratumab Antibodies | 0 percentage of participants |
| Olaratumab + Vincristine + Irinotecan (Part C) | Percentage of Participants With Treatment Emergent (TE) Positive Anti-Olaratumab Antibodies | 0 percentage of participants |
| Olaratumab + Ifosfamide (Part C) | Percentage of Participants With Treatment Emergent (TE) Positive Anti-Olaratumab Antibodies | 0 percentage of participants |
| Olaratumab + Doxorubicin (Part C) | Percentage of Participants With Treatment Emergent (TE) Positive Anti-Olaratumab Antibodies | 0 percentage of participants |
Secondary
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Olaratumab Part A
Pharmacokinetics (PK): Maximum serum concentration (Cmax) data of Olaratumab was reported from available sample data.
Time frame: Cycle 1, Day 8 and Cycle 2, Days 1 and 8: 1.25 hour (h), 2.5 h, 3.5h Postdose
Population: All participants who had evaluable PK individual serum concentration samples analyzed for Cycle 1 Olaratumab alone and Cycle 2 Olaratumab combinations for Part A.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Olaratumab + Vincristine + Irinotecan (Part A) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Olaratumab Part A | Cycle 1, Day 8 | 439 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 23 |
| Olaratumab + Ifosfamide (Part A) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Olaratumab Part A | Cycle 2, Day 1 | 406 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 21 |
| Olaratumab + Ifosfamide (Part A) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Olaratumab Part A | Cycle 2, Day 8 | 422 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 30 |
| Olaratumab + Doxorubicin (Part A) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Olaratumab Part A | Cycle 2, Day 8 | 398 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 44 |
| Olaratumab + Doxorubicin (Part A) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Olaratumab Part A | Cycle 2, Day 1 | 396 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 39 |
| Olaratumab + Vincristine + Irinotecan (Part B) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Olaratumab Part A | Cycle 2, Day 1 | 437 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 44 |
| Olaratumab + Vincristine + Irinotecan (Part B) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Olaratumab Part A | Cycle 2, Day 8 | 523 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 26 |
Secondary
PK: Maximum Concentration (Cmax) of Olaratumab Part B
PK: Maximum serum concentration (Cmax) data of Olaratumab was reported from available sample data.
Time frame: Cycle 1, Day 8 and Cycle 2, Days 1 and 8: 1.25 hour (h), 2.5 h, 3.5h Postdose
Population: All participants who had evaluable PK individual serum concentration samples analyzed for Cycle 1 Olaratumab alone and Cycle 2 Olaratumab combinations for Part B. Zero participants analyzed for Olaratumab and Doxorubicin being below the quantifiable limit.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Olaratumab + Vincristine + Irinotecan (Part A) | PK: Maximum Concentration (Cmax) of Olaratumab Part B | Cycle 1, Day 8 | 639 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 27 |
| Olaratumab + Doxorubicin (Part A) | PK: Maximum Concentration (Cmax) of Olaratumab Part B | Cycle 2, Day 1 | 629 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 32 |
| Olaratumab + Doxorubicin (Part A) | PK: Maximum Concentration (Cmax) of Olaratumab Part B | Cycle 2, Day 8 | 696 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 27 |
| Olaratumab + Vincristine + Irinotecan (Part B) | PK: Maximum Concentration (Cmax) of Olaratumab Part B | Cycle 2, Day 1 | 585 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 30 |
| Olaratumab + Vincristine + Irinotecan (Part B) | PK: Maximum Concentration (Cmax) of Olaratumab Part B | Cycle 2, Day 8 | 647 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 27 |
Secondary
PK: Maximum Concentration (Cmax) of Olaratumab Part C
Pharmacokinetics (PK): Maximum serum concentration (Cmax) data of Olaratumab was reported from available sample data.
Time frame: Cycle 1, Days 1 and 8; Cycle 2, Days 1 and 8: 1.25 hour (h), 2.5 h, 3.5h Postdose
Population: All participants who had evaluable PK individual serum concentration samples analyzed for Cycle 1 and 2 for all Part C treatment combinations. Per protocol, the Part C olaratumab alone was not collected.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Olaratumab + Vincristine + Irinotecan (Part A) | PK: Maximum Concentration (Cmax) of Olaratumab Part C | Cycle 1, Day 8 | 493 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 20 |
| Olaratumab + Vincristine + Irinotecan (Part A) | PK: Maximum Concentration (Cmax) of Olaratumab Part C | Cycle 1, Day 1 | 406 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 20 |
| Olaratumab + Ifosfamide (Part A) | PK: Maximum Concentration (Cmax) of Olaratumab Part C | Cycle 2, Day 8 | 502 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 38 |
| Olaratumab + Doxorubicin (Part A) | PK: Maximum Concentration (Cmax) of Olaratumab Part C | Cycle 1, Day 8 | 695 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 37 |
| Olaratumab + Doxorubicin (Part A) | PK: Maximum Concentration (Cmax) of Olaratumab Part C | Cycle 1, Day 1 | 548 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 15 |
| Olaratumab + Doxorubicin (Part A) | PK: Maximum Concentration (Cmax) of Olaratumab Part C | Cycle 2, Day 8 | 707 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 3 |
| Olaratumab + Vincristine + Irinotecan (Part B) | PK: Maximum Concentration (Cmax) of Olaratumab Part C | Cycle 1, Day 1 | 363 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 39 |
| Olaratumab + Vincristine + Irinotecan (Part B) | PK: Maximum Concentration (Cmax) of Olaratumab Part C | Cycle 2, Day 8 | 567 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 38 |
| Olaratumab + Vincristine + Irinotecan (Part B) | PK: Maximum Concentration (Cmax) of Olaratumab Part C | Cycle 1, Day 8 | 498 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 43 |
Secondary
PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part A
PK: Trough serum concentration (Cmin) of Olaratumab was reported. A sample was collected every other cycle from cycles 1, 2, 3-25.
Time frame: Cycles 1, 2, 3-25; Day 8: 336 Hours Postdose
Population: All participants who had evaluable PK individual serum concentration samples analyzed for Cycle 1 Olaratumab alone and Cycle 2 and 3-25 Olaratumab combinations for Part A.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Olaratumab + Vincristine + Irinotecan (Part A) | PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part A | Cycle 1, Day 8 | 73 μg/mL | Geometric Coefficient of Variation 56 |
| Olaratumab + Ifosfamide (Part A) | PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part A | Cycle 2, Day 8 | 38.5 μg/mL | Geometric Coefficient of Variation 29.1 |
| Olaratumab + Ifosfamide (Part A) | PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part A | Cycle 3-25, Day 8 | 94.4 μg/mL | Geometric Coefficient of Variation 41 |
| Olaratumab + Doxorubicin (Part A) | PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part A | Cycle 2, Day 8 | 114 μg/mL | Geometric Coefficient of Variation 85 |
| Olaratumab + Doxorubicin (Part A) | PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part A | Cycle 1, Day 8 | 46.3 μg/mL | Geometric Coefficient of Variation 284 |
| Olaratumab + Doxorubicin (Part A) | PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part A | Cycle 3-25, Day 8 | 88.2 μg/mL | Geometric Coefficient of Variation 77 |
| Olaratumab + Vincristine + Irinotecan (Part B) | PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part A | Cycle 1, Day 8 | 97.8 μg/mL | Geometric Coefficient of Variation 29 |
| Olaratumab + Vincristine + Irinotecan (Part B) | PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part A | Cycle 3-25, Day 8 | 95.1 μg/mL | Geometric Coefficient of Variation 85 |
| Olaratumab + Vincristine + Irinotecan (Part B) | PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part A | Cycle 2, Day 8 | 37.7 μg/mL | Geometric Coefficient of Variation 112 |
Secondary
PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part B
PK: Trough serum concentration (Cmin) of Olaratumab was reported. A sample was collected every other cycle from cycles 1, 2, 3-25.
Time frame: Cycles 1, 2, 3-25; Day 8: 336 Hours Postdose
Population: All participants who had evaluable PK individual serum concentration samples analyzed for Cycle 1, 2 and Cycle 3-25 Olaratumab combinations for Part B.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Olaratumab + Doxorubicin (Part A) | PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part B | Cycle 3-25, Day 8 | 289 μg/mL | Geometric Coefficient of Variation 14 |
| Olaratumab + Doxorubicin (Part A) | PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part B | Cycle 1, Day 8 | 125 μg/mL | Geometric Coefficient of Variation 55 |
| Olaratumab + Doxorubicin (Part A) | PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part B | Cycle 2, Day 8 | 199 μg/mL | Geometric Coefficient of Variation 36 |
| Olaratumab + Vincristine + Irinotecan (Part B) | PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part B | Cycle 1, Day 8 | 99.1 μg/mL | Geometric Coefficient of Variation 65 |
| Olaratumab + Vincristine + Irinotecan (Part B) | PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part B | Cycle 2, Day 8 | 230 μg/mL | Geometric Coefficient of Variation 17 |
| Olaratumab + Vincristine + Irinotecan (Part B) | PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part B | Cycle 3-25, Day 8 | 348 μg/mL | Geometric Coefficient of Variation 15 |
Secondary
PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part C
PK: Trough serum concentration (Cmin) of Olaratumab was reported. A sample was collected every other cycle from cycles 1, 2, 3-25.
Time frame: Cycles 1, 2, 3-25; Day 8: 336 Hours Postdose
Population: All participants who had evaluable PK individual serum concentration samples analyzed for Cycle 1, 2 and Cycle 3-25 Olaratumab combinations for Part C.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Olaratumab + Vincristine + Irinotecan (Part A) | PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part C | Cycle 2, Day 8 | 141 μg/mL | Geometric Coefficient of Variation 18 |
| Olaratumab + Vincristine + Irinotecan (Part A) | PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part C | Cycle 1, Day 8 | 90.3 μg/mL | Geometric Coefficient of Variation 33 |
| Olaratumab + Vincristine + Irinotecan (Part A) | PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part C | Cycle 3-25, Day 8 | 156 μg/mL | Geometric Coefficient of Variation 24 |
| Olaratumab + Ifosfamide (Part A) | PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part C | Cycle 2, Day 8 | 134 μg/mL | Geometric Coefficient of Variation 54 |
| Olaratumab + Ifosfamide (Part A) | PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part C | Cycle 1, Day 8 | 83.7 μg/mL | Geometric Coefficient of Variation 8 |
| Olaratumab + Ifosfamide (Part A) | PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part C | Cycle 3-25, Day 8 | 83.7 μg/mL | Geometric Coefficient of Variation 48 |
| Olaratumab + Doxorubicin (Part A) | PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part C | Cycle 1, Day 8 | 124 μg/mL | Geometric Coefficient of Variation 32 |
| Olaratumab + Doxorubicin (Part A) | PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part C | Cycle 3-25, Day 8 | NA μg/mL | — |
| Olaratumab + Doxorubicin (Part A) | PK: Trough Serum Minimum Concentration (Cmin) of Olaratumab Part C | Cycle 2, Day 8 | NA μg/mL | — |
Secondary
Progression Free Survival (PFS)
Progression-free survival (PFS) is defined as the time from baseline to the first date of radiological disease progression or death due to any cause. Progressive disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). The appearance of one or more new lesions is also considered progression. 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: Baseline to radiological disease progression or death from any cause (Up to 2 Years)
Population: All participants who received at least one dose of study drug. Censored participants: Parts A-C include arms: Olaratumab + Vincristine + Irinotecan, Olaratumab + Ifosfamide and Olaratumab + Doxorubicin. Part A censored participants are 2, 2, and 2; Part B censored participants are 2, 2, and 1 and Part C censored participants are 2,1, and 4.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Olaratumab + Vincristine + Irinotecan (Part A) | Progression Free Survival (PFS) | 1.54 Months |
| Olaratumab + Ifosfamide (Part A) | Progression Free Survival (PFS) | 1.38 Months |
| Olaratumab + Doxorubicin (Part A) | Progression Free Survival (PFS) | 1.26 Months |
| Olaratumab + Vincristine + Irinotecan (Part B) | Progression Free Survival (PFS) | 1.28 Months |
| Olaratumab + Ifosfamide (Part B) | Progression Free Survival (PFS) | 1.25 Months |
| Olaratumab + Doxorubicin (Part B) | Progression Free Survival (PFS) | NA Months |
| Olaratumab + Vincristine + Irinotecan (Part C) | Progression Free Survival (PFS) | 4.07 Months |
| Olaratumab + Ifosfamide (Part C) | Progression Free Survival (PFS) | 4.88 Months |
| Olaratumab + Doxorubicin (Part C) | Progression Free Survival (PFS) | 5.52 Months |