A Dose Escalation Study of OMP-59R5 in Subjects With Solid Tumors

Inclusion Criteria:

1. Subjects must have a histologically confirmed malignancy that is metastatic or unresectable for which there is no remaining standard curative therapy and no therapy with a demonstrated survival benefit. 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.
2. 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.
3. Age >18 years
4. ECOG performance status <2 (see Appendix B)
5. Life expectancy of more than 3 months

6. Subjects must have normal organ and marrow function as defined below:

   • Absolute neutrophil count >1000/mL
   • Hemoglobin >9.0 g/dL
   • Platelets >100,000/mL
   • 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 for subjects with creatinine levels above institutional normal
7. 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 (hormonal or 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.
8. Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

1. Subjects receiving any other investigational agents
2. 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
3. History of a significant allergic reaction attributed to humanized or human monoclonal antibody therapy
4. 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
5. Pregnant women or nursing women
6. Subjects with known HIV infection
7. Known bleeding disorder or coagulopathy
8. 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.
9. New York Heart Association Classification II, III, or IV
10. Subjects with a blood pressure of >140/90 mmHg. The blood pressure must be taken three times 10 minutes apart. Subjects taking antihypertensive medications must be taking ≤ 2 medications to obtain this level of blood pressure control.
11. Subjects with EKG evidence of ischemia or ≥ Grade 2 ventricular arrhythmia, subjects who have a history of acute myocardial infarction within 6 months, or subjects with unstable angina.
12. Subjects with known clinically significant gastrointestinal disease including, but not limited to, inflammatory bowel disease.
13. Subjects with known clinically significant gastrointestinal disease including, but not limited to, inflammatory bowel disease.
14. Subjects with >1 grade 1 diarrhea.