A Phase 1 Study of OMP-305B83 in Subjects With Solid Tumors

This is an open-label Phase 1 dose escalation and expansion study of OMP-305B83 in subjects
with previously treated solid tumors. Study includes a dose escalation phase and expansion
phase. Subjects will be assessed for safety, immunogenicity, pharmacokinetics, biomarkers,
and efficacy.

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 or they must be ineligible to receive such
therapy and/or have declined all such therapy. 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. FFPE tumor tissue either fresh core needle biopsied or archived (two FFPE cores
preferred whenever possible) is required for participation in the study. If fresh
tissue is obtained, the core biopsy must be done at least ≥7 days prior to Day 0.

3. Subjects must have received their last chemotherapy, non-anti-VEGF biologic, or
investigational therapy at least 4 weeks prior to enrollment, 6 weeks if the last
regimen included BCNU or mitomycin C, and 8 weeks if the last regimen was an anti-VEGF
therapy

4. Age >21 years

5. ECOG performance status <2

6. Life expectancy of more than 3 months

7. Subjects must have adequate organ and marrow function as defined below:

- Absolute neutrophil count >1000/mL (without a colony stimulating factor within
the last 2 weeks)

- Hemoglobin >10.5 g/dL (without erythropoietin or blood transfusion within the
last 2 weeks)

- Platelets >100,000/mL (without platelet transfusion within the last 2 weeks)

- Total bilirubin <1.5 X institutional upper limit of normal (ULN)

- AST (SGOT) and ALT (SGPT) <2 X institutional ULN (for subjects with hepatic
metastases <5 X institutional ULN)

- INR and PTT within 1.5 X institutional ULN

- Proteinuria < trace

- Creatinine <1.5 X institutional ULN OR

- Creatinine clearance >60 mL/min/1.73 m2 for subjects with creatinine levels above
institutional normal

8. 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.

9. Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

1. Subjects receiving any other investigational agents

2. Subjects who have received an anti-DLL4 antibody, or an anti-DLL4/VEGF bispecific
antibody Subjects who have received prior anti-VEGF therapy are eligible, unless they
have residual serious adverse events related to their anti-VEGF therapy.

3. Subjects with a history of abdominal fistula, gastrointestinal perforation,
intra-abdominal abscess; clinical signs or symptoms of GI obstruction and/or
requirement for parenteral hydration or nutrition. In addition, subjects with other
known clinically significant gastrointestinal disease including, but not limited to,
inflammatory bowel disease.

4. 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

5. History of a significant allergic reaction attributed to humanized or human monoclonal
antibody therapy

6. 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

7. Pregnant women or nursing women

8. Subjects with known HIV infection

9. Known bleeding disorder or coagulopathy

10. 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.

11. Subjects with ascites or pleural effusion requiring drainage within the last 28 days.

12. Subjects with a blood pressure of >140/90 mmHg.

13. Subjects with squamous cell carcinoma of the lung

14. Subjects having undergone a major surgery within the last 6 weeks

15. New York Heart Association Classification II, III, or IV (see APPENDIX D)