Study of A166 in Patients With Relapsed/Refractory Cancers Expressing HER2 Antigen or Having Amplified HER2 Gene

Exclusion Criteria

• •Phase I:
• •1. Severe or uncontrolled cardiac disease requiring treatment, congestive heart failure (New York Heart Association) III or IV, unstable angina pectoris even if medically controlled, history of myocardial infarction during the last 6 months, serious arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal supraventricular tachycardia).
• •2. History of Grade ≥ 3 hypersensitivity reaction to trastuzumab.
• •3. History of any toxicity to trastuzumab that resulted in trastuzumab being permanently discontinued.
• •4. Symptomatic brain metastases or any radiation or surgery for brain metastases within 3 months of first infusion of study drug.
• •5. Require supplemental oxygen for daily activities.
• •6. Documented Grade ≥ 2 peripheral neuropathy.
• •7. Any chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or biologic therapy treatment within 4 weeks of first infusion of study drug.
• •8. Any experimental therapy within 4 weeks of first infusion of study drug.
• •9. Any major surgical procedure within 4 weeks of first infusion of study drug.
• •10. Diagnosed active liver disease, including viral or other hepatitis, current or history of alcoholism, or cirrhosis. Patients who have positive hepatitis B virus test results due to having been previously vaccinated against hepatitis B, as evidenced by negative hepatitis B surface antigen (HBsAg), negative anti hepatitis B core protein, and positive antibody to the HBsAg (anti-HBs) are not excluded.
• •11. Have known prior positive test results for human immunodeficiency virus.
• •12. Uncontrolled hypertension or diabetes.
• •13. Pregnancy or lactation.
• •14. Resting corrected QT interval (QTc) \> 470 ms at baseline.
• •15. Left ventricular ejection fraction (LVEF) \< 45% determined by echocardiogram (ECHO) or multigated acquisition (MUGA) scan.
• •16. Prior cumulative doxorubicin dose of \> 360 mg/m2 or equivalent.