A Phase 1a/b Dose Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of OMP-131R10

The Phase 1a portion of the study in subjects with advanced solid tumors will consist of a
dose escalation part followed by a dose-expansion cohort. OMP-131R10 will be administered IV
on the first day of each 14-day cycle.

Dose escalation will follow a traditional 3+3 framework. Treatment will be continued until
progressive disease or unacceptable toxicity.

The Phase 1b portion of the study will be conducted in subjects with metastatic colorectal
cancer whose tumors have progressed after at least 1 line of therapy for metastatic disease.

Treatment will consist of OMP-131R10 and the FOLFIRI chemotherapy regimen.

Inclusion Criteria:

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

1. Phase 1a portion: Histologically confirmed advanced relapsed or refractory solid
tumors that have exhausted standard of care therapy or either refuse or are not
considered to be candidates for any remaining standard therapy.

2. Age ≥18 years

3. ECOG performance status 0 or 1 (see Appendix B)

4. Must have evaluable disease per RECIST 1.1. (see Appendix C)

5. Subjects must have Formalin-Fixed, Paraffin-Embedded (FFPE) tissue available either
archived or fresh core or punch needle biopsied at study entry (two fresh
cores/punches preferred whenever possible).

6. Must have received their last anti-cancer therapy, including radiotherapy,
chemotherapy, biologic therapy, or herbal therapy at least 3 weeks or 5 half-lives
(for systemic agents), whichever is shorter, from initiation of study treatment.

7. Platelets >100,000/mL without transfusions in the past 7 days

8. Total bilirubin within 1.5x institutional upper limit of normal (ULN)

- AST (SGOT) and ALT (SGPT) <3 X institutional ULN

- Patients with documented liver metastases: AST (SGOT) and/or ALT (SGPT) ≤ 5 × ULN

- Albumin ≥ 3.0 g/dL

- Creatinine <1.5 X institutional ULN OR

- Creatinine clearance >50 mL/min/1.73 m2 for subjects with creatinine levels above
institutional normal

Exclusion Criteria:

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

1. Currently receiving any therapeutic treatment for their malignancy including other
investigational agents

2. Uncontrolled seizure disorder, active neurologic disease, or active CNS involvement
except for individuals who have previously treated CNS metastases, are asymptomatic,
and have no requirement for a corticosteroid dose (indicated to reduce brain edema)
that is equivalent to a prednisone dose of >10mg orally per day or anti-seizure
medication for at least 4 weeks prior to first dose of study drug.

3. History of a Grade 3 or 4 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 congestive heart failure with New York Heart Association Classification
III, or IV (see Appendix D)

7. Known clinically significant gastrointestinal disease including, but not limited to,
inflammatory bowel disease