Study to Assess Pharmacokinetics, Immunogenicity and Safety/Tolerability of Patritumab (U3-1287)

Exclusion Criteria

• •Have a history of lymphoma, leukemia, or other hematopoietic malignancy.
• •Have Have autologous or allogeneic stem cell transplant.
• •Have any comorbid medical condition that would increase the risk of toxicity in the opinion of the investigator or sponsor.
• •Have untreated or symptomatic brain metastasis.
• •Have uncontrolled hypertension (diastolic blood pressure \> 100 mmHg or systolic blood pressure \> 140 mmHg). It is permissible for the subject to receive treatment with antihypertensive medication to maintain blood pressure within the required parameters.
• •Have clinically significant ECG changes that obscure the ability to assess the RR, PR, QT, QT interval corrected for heart rate (QTc), and QRS interval. Subjects with left bundle branch block, atrial fibrillation and use of cardiac pacemaker specifically will be excluded.
• •Have ascites or pleural effusion requiring chronic medical intervention.
• •Have a history of bleeding diathesis.
• •Have had a myocardial infarction within 1 year before enrollment, symptomatic CHF (New York Heart Association \> Class II;), unstable angina, or unstable cardiac arrhythmia requiring medication.
• •Use of amiodarone within 6 months prior to enrollment.
• •Concurrent use of antiarrhythmic medications with the exception of beta blockers for treatment of hypertension.
• •Subjects who are receiving drugs that may affect QTc (e.g., quinidine or moxifloxacin).
• •QTc interval \> 450 msec on the average of the triplicate readings by Friderica's formula on 2 successive screening measurements (second measurement is required if first measurement is \> 450 msec).
• •Have a LVEF \< 50%.
• •Have anthracycline exposure greater than 360 mg/m2.
• •Have a history of chronic hepatitis or known active infection with hepatitis B virus or hepatitis C virus.
• •Personal or family history of long-QT syndrome.
• •Have known infection with or a history of testing positive for human immunodeficiency virus (HIV).
• •Had treatment with anticancer therapy (6 weeks for nitrosoureas and mitomycin C chemotherapies and 2 weeks for small molecule tyrosine kinase inhibitors), antibody therapy, retinoid therapy, or hormonal therapy within 4 weeks before study Day 1. Prior and concurrent use of hormone replacement therapy or the use of gonadotropin releasing hormone modulators for prostate cancer is permitted.
• •Had therapeutic or palliative radiation therapy within 4 weeks before enrollment (in addition, he/she must have had resolution of any significant AEs from radiation therapy at least 2 weeks before enrollment).
• •Have concurrent or previous (within 1 week of study Day 1) anticoagulation therapy, except low-dose warfarin (≤ 2 mg/day) or low-dose, low-molecular weight heparin for prophylaxis against central venous catheter thrombosis or deep vein thrombosis.
• •Have participated in clinical drug trials within 4 weeks before enrollment.
• •Have had major surgery within 4 weeks before enrollment.
• •Is currently participating in other investigational procedures.
• •Has any disorder that compromised the ability of the subject to give written informed consent and/or comply with study procedures.
• •Has known sensitivity to any of the products to be administered during dosing or known allergy to the excipients or investigational drugs.
• •Has active infection within 2 weeks before enrollment unless there was a discussion with the sponsor and an agreement was reached that the recent infection would not affect the subject's participation in the study.
• •Has previously received an anti-HER3 targeted antibody, including patritumab.