A Phase 1 study of AMG 208 in subjects with advanced solid tumors

-Men or women ≥ 18 years old -Subjects must have a pathologically documented, definitively diagnosed, advanced solid tumor that is refractory to standard treatment, for which no standard therapy is available or the subject refuses standard therapy -Measurable disease per RECIST guidelines (subjects with non-measurable, but evaluable disease are also eligible for Part 1 of the study) -Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2 -Life expectancy of > 3 months, in the opinion of the investigator -Female subjects who are post-menopausal (no menstrual period for a minimum of 12 months), or surgically sterilized. Female subjects of child bearing potential must remain abstinent or use double-barrier birth control method during the period of therapy and must be willing to use contraception 2 weeks following the last study drug administration and have a negative serum pregnancy test upon entry into this study -Male subject is willing to use contraception upon enrollment, during the course of the study and for 12 weeks following the last study drug administration -Willing to provide tumor samples and / or slides -Competent to sign and date an Institutional Review Board approved informed consent form -Hematological function, as follows: Absolute neutrophil count (ANC) ≥ 1.5 x 109/L Platelet count ≥ 100 x 109/L Hemoglobin > 9 g/dL Prothrombin time (PT) or partial thromboplastin time (PTT) < 1.5 x institutional upper limit of normal (IULN) -Renal function, as follows: Serum creatinine < 2.0 mg/dL -Hepatic function, as follows: AST/ALT < 3x ULN and total bilirubin < 1.5x ULN in all subjects Alkaline phosphatase < 2.0 x ULN (if liver or bone metastases are present, ≤ 5 x ULN)

-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