A Dose Escalation Study of OMP-54F28 in Subjects With Solid Tumors

Inclusion criteria

Subjects must meet all of the following criteria to be eligible for the study:

• Subjects must have a histologically confirmed malignancy that is metastatic or unresectable and must have received the standard therapies for their malignancy. In addition, subjects must have a tumor that is at least 1 cm in a single dimension and is radiographically apparent on CT or MRI.
• Subjects must have received their last chemotherapy, biologic, or investigational therapy at least 4 weeks prior to enrollment, 6 weeks if the last regimen included BCNU or mitomycin C.
• Age >18 years
• ECOG performance status <2 (see APPENDIX B)
• Estimated life expectancy of more than 3 months
• Subjects must have adequate organ and marrow function as defined below:

Absolute neutrophil count >1000/µL Hemoglobin >9.0 g/dL Platelets >100,000/µL Total bilirubin <1.5 X institutional upper limit of normal (ULN) AST (SGOT) and ALT (SGPT) <3 X institutional ULN (for subjects with hepatic metastases <5 X institutional ULN) PT and PTT within 1.5 X institutional ULN Creatinine <1.5 X institutional ULN OR Creatinine clearance >60 mL/min/1.73 m2

• Women of childbearing potential must have had a prior hysterectomy or have a negative serum pregnancy test and be using adequate contraception prior to study entry and must agree to use adequate contraception from study entry through at least 6 months after discontinuation of study drug. Men must also agree to use adequate contraception (barrier method of birth control, abstinence) prior to study entry and from study entry through at least 6 months after discontinuation of study drug. Should a woman enrolled in the study or a female partner of a man enrolled in the study become pregnant or suspect she is pregnant while participating in this study or within 6 months after discontinuation of study, she should inform the Investigator immediately.
• Ability to understand and the willingness to sign a written informed consent document

Exclusion criteria

Subjects who meet any of the following criteria will not be eligible for participation in the study:

• Subjects receiving any other investigational agents
• Subjects with brain metastases (subjects must have a CT scan or MRI of the head within 28 days prior to enrollment to rule out brain metastases), uncontrolled seizure disorder, or active neurologic disease
• History of a significant allergic reaction attributed to humanized or human monoclonal antibody therapy or Fc fusion protein
• Significant intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women or nursing women
• Subjects with known HIV, Hepatitis B or Hepatitis C infection
• Known bleeding disorder or coagulopathy
• Subjects receiving heparin, warfarin, or other similar anticoagulants, except for subjects on low molecular weight heparin for DVT/PE prophylaxis. Note: Subjects may be receiving low-dose aspirin and/or non-steroidal anti-inflammatory agents.
• New York Heart Association Classification III, or IV (see APPENDIX D)
• Subjects with known clinically significant gastrointestinal disease including, but not limited to, inflammatory bowel disease.
• Subjects with osteopenia or osteoporosis on their screening DEXA bone density scan.
• Subjects with bone metastases that:

• have a prior history of a pathologic fracture,
• have a lytic lesion requiring an orthopedic intervention or
• are not receiving a bisphosphonate zoledronic acid or denosumab as per institutional guidelines All other subjects with bone metastases are eligible.
• Subjects receiving a thiazolidinedione PPAR gamma inhibitor; i.e. Actos® (pioglitazone), Avandia® (rosiglitazone), and Rezulin® (troglitazone).
• Subjects who have received ≥4 weeks of an oral or intravenous glucocorticoid at a dose that is equivalent to or greater than 5 mg of oral prednisone within the last 8 weeks.
• Subjects with a fasting β-CTX of >1000 pg/mL.
• Subjects with metabolic bone disease, such as hyperparathyroidism, Paget's disease or osteomalacia.
• Subjects with a history of or a newly diagnosed insufficiency fracture or morphometric (asymptomatic) vertebral fracture on the screening lateral lumbosacral spine film.