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| ID | Type | Description | Link |
|---|---|---|---|
| CP15-0907 | Other Identifier | ImClone, LLC | |
| I5B-IE-JGDF | Other Identifier | Eli Lilly and Company | |
| 21-3720 | Other Identifier | PMDA (MoH) in Japan |
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Participants in this single-center, open-label, dose-escalation, Phase 1 study will initially receive intravenous (IV) olaratumab once every 2 weeks or on Days 1 and 8 every 3 weeks for 6 weeks (one cycle). After the first cycle, participants experiencing an overall response of complete response (CR), partial response (PR), or stable disease (SD) will continue to receive olaratumab at their cohort dose and schedule until there is evidence of progressive disease (PD), or until other withdrawal criteria are met.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Olaratumab | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Olaratumab | Biological | Cohort 1 10 milligrams/kilogram (mg/kg) intravenously (IV) administered on Days 1 and 8, every 3 weeks; Cohort 2 20 mg/kg IV administered every 2 weeks; Cohort 3 15 mg/kg IV administered on Days 1 and 8, every 3 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | Data presented are the number of participants who experienced AEs of any grade and AEs of Grade ≥3 as determined by National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v) 4.02. A summary of serious adverse events (SAEs) and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module. | First dose to study completion up to 5.6 months |
| Number of Participants With SAEs | A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module. | First dose to study completion up to 5.6 months |
| Number of Participants With a Dose- Limiting Toxicity (DLT) in Cycle 1 | A DLT is defined as 1 of the following events, if considered by the investigator to be definitely, probably, or possibly related to olaratumab: NCI-CTCAE v4.02 Grade 4 neutropenia lasting >7 days; NCI-CTCAE v4.02 Grade ≥3 thrombocytopenia with signs of bleeding or requiring platelet transfusions; NCI-CTCAE v4.02 Grade ≥3 neutropenia associated with fever; NCI-CTCAE v4.02 Grade 3 or 4 nonhematologic toxicity, excluding electrolyte abnormality; NCI-CTCAE v4.02 Grade ≥3 skin toxicity despite best preemptive and supportive care; and/or NCI-CTCAE v4.02 Grade ≥3 diarrhea, nausea, or vomiting despite best preemptive and supportive care. | First dose through Cycle 1 (6 weeks/cycle) |
| Maximum Concentration (Cmax) of Olaratumab Following Multiple Doses | Cycle 2: Pre-dose and up to 336 hours post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Concentration of Olaratumab Versus Time Curve During One Dosing Interval (AUCτ) Following Multiple Doses | Cycle 2: Pre-dose and up to 336 hours post-dose | |
| Terminal Elimination Half-Life (t1/2) of Olaratumab | t1/2 is the time it takes for the drug concentration in serum to decrease to half the value observed at the beginning of the time period. |
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Inclusion Criteria:
Exclusion Criteria:
Received chemotherapy or therapeutic radiotherapy within 28 days (6 weeks for nitrosoureas or mitomycin C) prior to entering the study, or has ongoing side effects ≥ Grade 2 due to agents administered more than 28 days earlier
Has undergone major surgery [example (e.g.), laparotomy, thoracotomy, removal of organ(s)] within 28 days prior to study entry
Elective or planned surgery to be conducted during the trial
Documented and/or symptomatic brain or leptomeningeal metastases (participants who are clinically stable [no symptoms during the 4 weeks prior to study entry] with an assessment that no further treatment [radiation, surgical excision, or administration of steroids] is required are permitted to enter the study)
Uncontrolled intercurrent illness including, but not limited to:
Participated in clinical studies of non-approved experimental agents or procedures within 4 weeks prior to study for small molecules, or 8 weeks prior to study entry for non-approved monoclonal antibodies
Received any previous treatment with agents targeting the platelet-derived growth factor (PDGF) or platelet-derived growth factor receptor (PDGFR), approved or non-approved
Known allergy to any of the treatment components (IMC-3G3, histidine, glycine, sodium chloride, mannitol, or polysorbate)
If female, is pregnant (confirmed by urine or serum pregnancy test) or lactating
Known alcohol or drug dependency
Hepatitis B virus (HBV) antigen-, hepatitis C virus (HCV) antibody-, or human immunodeficiency (HIV) antibody-positive [asymptomatic healthy carriers with detectable HBV-Deoxyribonucleic acid (DNA), HCV-Ribonucleic acid (RNA) may be enrolled into the trial]
Assessed as inadequate for the study by the investigator](streamdown:incomplete-link)
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| Name | Affiliation | Role |
|---|---|---|
| Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) | Eli Lilly and Company | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| ImClone Investigational Site | Kashiwa | Chiba | Japan |
There were 3 cohorts and enrollment into the next cohort did not occur until all participants in the previous cohort completed 1 cycle of treatment or discontinued due to dose-limiting toxicity (DLT). Participants who completed Cycle 1 or had DLT during Cycle 1 are considered having completed study.
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| ID | Title | Description |
|---|---|---|
| FG000 | 10 mg/kg Olaratumab (IMC-3G3) | 10 milligrams/kilogram (mg/kg) olaratumab intravenously (IV) administered on Days 1 and 8, every 3 weeks (6-week cycle). Cycles repeated until there was evidence of progressive disease (PD), or until other withdrawal criteria were met. |
| FG001 | 20 mg/kg Olaratumab | 20 mg/kg olaratumab IV administered on Day 1 every 2 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met. |
| FG002 | 15 mg/kg Olaratumab | 15 mg/kg olaratumab IV administered on Days 1 and 8, every 3 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
All enrolled participants who received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | 10 mg/kg Olaratumab | 10 mg/kg olaratumab IV administered on Days 1 and 8, every 3 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met. |
| BG001 | 20 mg/kg Olaratumab |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Number |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Adverse Events (AEs) | Data presented are the number of participants who experienced AEs of any grade and AEs of Grade ≥3 as determined by National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v) 4.02. A summary of serious adverse events (SAEs) and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module. | All enrolled participants who received at least 1 dose of study drug. | Posted | Number | participants | First dose to study completion up to 5.6 months |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 10 mg/kg Olaratumab | 10 mg/kg olaratumab IV administered on Days 1 and 8, every 3 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Tumour haemorrhage | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 12.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 12.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Eli Lilly and Company | 800-545-5979 |
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| ID | Term |
|---|---|
| D009369 | Neoplasms |
| D009362 | Neoplasm Metastasis |
| ID | Term |
|---|---|
| D009385 | Neoplastic Processes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C000589393 | olaratumab |
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|
| Cycle 2: Pre-dose and up to 336 hours post-dose |
| Clearance of Olaratumab at Steady State (CLss) | CLss is the volume of plasma (or blood) from which the drug is completely removed, or cleared, in a given time at steady-state. | Cycle 2: Pre-dose and up to 336 hours post-dose |
| Volume of Distribution at Steady State (Vss) | Cycle 2: Pre-dose and up to 336 hours post-dose |
| Number of Participants With Serum Anti-Olaratumab Antibody Assessment (Immunogenicity) | 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. | First dose to study completion up to 5.6 months |
| Number of Participants With Treatment Related AEs | Data presented are the number of participants who experienced a treatment related AE of any grade. | First dose to study completion up to 5.6 months |
20 mg/kg olaratumab IV administered on Day 1 every 2 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.
| BG002 | 15 mg/kg Olaratumab | 15 mg/kg olaratumab IV administered on Days 1 and 8, every 3 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met. |
| BG003 | Total | Total of all reporting groups |
| participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| 20 mg/kg Olaratumab |
20 mg/kg olaratumab IV administered on Day 1 every 2 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met. |
| OG002 | 15 mg/kg Olaratumab | 15 mg/kg olaratumab IV administered on Days 1 and 8, every 3 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met. |
|
|
| Primary | Number of Participants With SAEs | A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module. | All enrolled participants who received at least 1 dose of study drug. | Posted | Number | participants | First dose to study completion up to 5.6 months |
|
|
|
| Primary | Number of Participants With a Dose- Limiting Toxicity (DLT) in Cycle 1 | A DLT is defined as 1 of the following events, if considered by the investigator to be definitely, probably, or possibly related to olaratumab: NCI-CTCAE v4.02 Grade 4 neutropenia lasting >7 days; NCI-CTCAE v4.02 Grade ≥3 thrombocytopenia with signs of bleeding or requiring platelet transfusions; NCI-CTCAE v4.02 Grade ≥3 neutropenia associated with fever; NCI-CTCAE v4.02 Grade 3 or 4 nonhematologic toxicity, excluding electrolyte abnormality; NCI-CTCAE v4.02 Grade ≥3 skin toxicity despite best preemptive and supportive care; and/or NCI-CTCAE v4.02 Grade ≥3 diarrhea, nausea, or vomiting despite best preemptive and supportive care. | All enrolled participants who received at least 1 dose of study drug. | Posted | Number | participants | First dose through Cycle 1 (6 weeks/cycle) |
|
|
|
| Primary | Maximum Concentration (Cmax) of Olaratumab Following Multiple Doses | All participants who received study drug and had pharmacokinetic (PK) data available to calculate Cmax. Due to the limited data, Cmax is not representative of the study population. | Posted | Geometric Mean | Geometric Coefficient of Variation | micrograms/milliliter (µg/mL) | Cycle 2: Pre-dose and up to 336 hours post-dose |
|
|
|
| Secondary | Area Under the Concentration of Olaratumab Versus Time Curve During One Dosing Interval (AUCτ) Following Multiple Doses | All participants who received study drug and had PK data available to calculate AUCτ. Zero participants were analyzed for groups of 10 mg/kg IMC-3G3 and 15 mg/kg IMC-3G3 because of insufficient amount of samples collected. Due to the limited data, AUCτ is not representative of the study population. | Posted | Geometric Mean | Geometric Coefficient of Variation | micrograms*hours/milliliter (µg*h/mL) | Cycle 2: Pre-dose and up to 336 hours post-dose |
|
|
|
| Secondary | Terminal Elimination Half-Life (t1/2) of Olaratumab | t1/2 is the time it takes for the drug concentration in serum to decrease to half the value observed at the beginning of the time period. | All participants who received study drug and had PK data available to calculate t1/2. Due to limited data and the relatively short duration of sample collection, t1/2 is not representative of the study population. | Posted | Geometric Mean | Full Range | days | Cycle 2: Pre-dose and up to 336 hours post-dose |
|
|
|
| Secondary | Clearance of Olaratumab at Steady State (CLss) | CLss is the volume of plasma (or blood) from which the drug is completely removed, or cleared, in a given time at steady-state. | All participants who received study drug and had PK data available to calculate CLss. Zero participants were analyzed for groups of 10 mg/kg IMC-3G3 and 15 mg/kg IMC-3G3 because of insufficient amount of samples collected. Due to limited data, CLss is not representative of the study population. | Posted | Geometric Mean | Geometric Coefficient of Variation | milliliters/hour/kilogram (mL/h/kg) | Cycle 2: Pre-dose and up to 336 hours post-dose |
|
|
|
| Secondary | Volume of Distribution at Steady State (Vss) | Zero participants were analyzed because of insufficient amount of samples collected. | Posted | Cycle 2: Pre-dose and up to 336 hours post-dose |
|
|
| Secondary | Number of Participants With Serum Anti-Olaratumab Antibody Assessment (Immunogenicity) | 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. | All participants who received at least one dose of study drug and had evaluable baseline and evaluable post-baseline antibody data. | Posted | Number | participants | First dose to study completion up to 5.6 months |
|
|
|
| Secondary | Number of Participants With Treatment Related AEs | Data presented are the number of participants who experienced a treatment related AE of any grade. | All enrolled participants who received at least 1 dose of study drug. | Posted | Number | participants | First dose to study completion up to 5.6 months |
|
|
|
| 0 |
| 3 |
| 3 |
| 3 |
| EG001 | 20 mg/kg Olaratumab | 20 mg/kg olaratumab IV administered on Day 1 every 2 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met. | 1 | 7 | 7 | 7 |
| EG002 | 15 mg/kg Olaratumab | 15 mg/kg olaratumab IV administered on Days 1 and 8, every 3 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met. | 0 | 6 | 6 | 6 |
| Leukopenia | Blood and lymphatic system disorders | MedDRA 12.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
|
| Periodontal disease | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 12.0 | Systematic Assessment |
|
| Malaise | General disorders | MedDRA 12.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 12.0 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 12.0 | Systematic Assessment |
|
| Fibrin D dimer increased | Investigations | MedDRA 12.0 | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA 12.0 | Systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | MedDRA 12.0 | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 12.0 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 12.0 | Systematic Assessment |
|
| Cancer pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 12.0 | Systematic Assessment |
|
| Cognitive disorder | Nervous system disorders | MedDRA 12.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 12.0 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 12.0 | Systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | MedDRA 12.0 | Systematic Assessment |
|
| Metrorrhagia | Reproductive system and breast disorders | MedDRA 12.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 12.0 | Systematic Assessment |
|
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA 12.0 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 12.0 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 12.0 | Systematic Assessment |
|
Investigators agreed to delay independently publishing or disclosing data, findings or conclusions from the study except as part of a multi-center publication. Upon study publication or if the draft publication is not produced within approximately 6 months of the final report of the study results, investigators may independently publish, subject to confidential information review/redaction by sponsor. The sponsor may request publication delay up to 90 days to seek patent protection.
| Title | Measurements |
|---|---|
|
| Leukopenia |
|
| Diarrhoea |
|
| Fatigue |
|
| Aspartate aminotransferase increased |
|
| Fibrin D dimer increased |
|
| Hyperglycaemia |
|
| Tumour haemorrhage |
|
| Proteinuria |
|
| Cough |
|
| Dermatitis |
|
| Rash |
|
| Hypertension |
|