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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
16
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
ImClone Investigational Site
Kashiwa, Chiba, Japan
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.
Time frame: 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.
Time frame: 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.
Time frame: First dose through Cycle 1 (6 weeks/cycle)
Maximum Concentration (Cmax) of Olaratumab Following Multiple Doses
Time frame: Cycle 2: Pre-dose and up to 336 hours post-dose
Area Under the Concentration of Olaratumab Versus Time Curve During One Dosing Interval (AUCτ) Following Multiple Doses
Time frame: 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.
Time frame: 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.
Time frame: Cycle 2: Pre-dose and up to 336 hours post-dose
Volume of Distribution at Steady State (Vss)
Time frame: 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.
Time frame: 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.
Time frame: First dose to study completion up to 5.6 months
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