Study of the Safety and Pharmacokinetics of Olaratumab (IMC-3G3) in Japanese Participants With Solid Tumors

Study Overview
=================
Brief Summary
-----------------
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.

Official Title
-----------------
A Phase 1 Study Evaluating the Safety and Pharmacokinetic Profiles of IMC-3G3 Administered in a 2-week, or 3-week Schedule to Japanese Patients With Advanced Solid Tumors

Conditions
-----------------
Malignancy, Metastasis

Intervention / Treatment
-----------------
* Biological: Olaratumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Solid tumor that has been histopathologically or cytologically documented Advanced primary or recurrent solid tumor participants who has not responded to standard therapy or for whom no standard therapy is available Measurable or nonmeasurable lesions An Eastern Cooperative Oncology Group Performance Status score of 0-1 Able to provide informed consent Has a life expectancy of >3 months Adequate hematologic function Adequate hepatic function Has adequate renal function Agrees to use adequate contraception for the duration of study participation and for at least 12 weeks after the last dose of study therapy Adequate recovery from recent surgery, chemotherapy, and radiation therapy (including palliative radiation therapy). At least 28 days (6 weeks for nitrosoureas or mitomycin C) must have elapsed from major surgery, prior chemotherapy, prior treatment with an investigational agent or device, or prior radiation therapy. For treatment with non-approved monoclonal antibodies, a minimum of 8 weeks must have elapsed Is willing to comply with study procedures until the End-of-Therapy visit 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: Active infection requiring systemic antibiotic treatment excluding oral administration [≥Grade 3 National Cancer Institute - Common Terminology Criteria for Adverse Events [NCI-CTCAE Version (v) 4.02)] Congestive heart failure (Class III or IV per the New York Heart Association classification for heart disease) Angina pectoris, angioplasty, stenting, or myocardial infarction within 6 months Uncontrolled hypertension [systolic blood pressure >150 millimeters of mercury (mm Hg), diastolic blood pressure >95 mm Hg] Cardiac arrhythmia requiring treatment (NCI-CTCAE v4.02, or asymptomatic sustained ventricular tachycardia Peripheral neuropathy of any etiology ≥Grade 2 (NCI-CTCAE v4.02); or Any other serious uncontrolled medical disorder(s) in the opinion of the investigator 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

Ages Eligible for Study
-----------------
Minimum Age: 20 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Olaratumab<br> | Biological: Olaratumab<br>* 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<br>* Other names: LY3012207;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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. | 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 |