A Phase 1 Study of AMG 208 in Subjects With Advanced Solid Tumors

Exclusion Criteria

• •Any disorder that compromises the ability of the subject to give written informed consent and/or to comply with the study procedures.
• •Primary central nervous system (CNS) tumors or metastases
• •History of bleeding diathesis
• •Myocardial infarction within 6 months of study day 1, symptomatic congestive heart failure (New York Heart Association \> class II), unstable angina, or unstable cardiac arrhythmia requiring medication, or uncontrolled hypertension in the opinion of the investigator
• •A baseline ECG QTc \> 480 ms
• •Active infection within 2 weeks of study enrollment (day 1)
• •Significant gastrointestinal disorder(s), in the opinion of the investigator, (e.g. Crohn's disease, ulcerative colitis, extensive gastrointestinal resection) that may influence drug absorption
• •Known positive test for HIV
• •Known acute or chronic hepatitis B or hepatitis C infection, determined by serologic tests
• •Unresolved toxicities from prior anti-tumor therapy, defined as not having resolved to CTCAE grade 0 or 1, or to levels dictated in the eligibility criteria with the exception of alopecia
• •Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy, retinoid therapy, hormonal therapy, or investigational agent) within 28 days of study day 1 (six weeks for nitrosureas, mitomycin C, or antibody or molecular targeted agents with t1/2 \> 10 days); concurrent use of hormone deprivation therapy for hormone-refractory prostate cancer or breast cancer is permitted
• •Treatment with immune modulators including, but not limited to, systemic corticosteroids, cyclosporine and tacrolimus within two weeks prior to enrollment
• •Therapeutic or palliative radiation therapy within 2 weeks of study day 1
• •Concurrent or prior (within 7 days of study day 1) anticoagulation therapy (low-dose warfarin \[≤ 2 mg/day\] or low molecular weight heparins for prophylaxis against central venous catheter thrombosis or aspirin \[81 mg/day\] is allowed)
• •Prior participation in an investigational study and/or procedure within 28 days of study day 1
• •Major surgery within 30 days of study day 1
• •Any co-morbid medical disorder that may increase the risk of toxicity, in the opinion of the investigator or sponsor