A Dose Escalation Study of OMP-18R5 in Subjects With Solid Tumors

Status:	Recruiting
Conditions:	Cancer
Therapuetic Areas:	Oncology
Healthy:	No
Age Range:	18 - 90
Updated:	5/5/2014
Start Date:	May 2011
End Date:	June 2016

A Phase 1 Dose Escalation Study of OMP-18R5 in Subjects With Solid Tumors

This is an open-label Phase 1 dose escalation study of OMP-18R5 in subjects with a solid
tumor for which there is no remaining standard curative therapy and no therapy with a
demonstrated survival benefit. Up to 44 subjects will be enrolled at up to 2 centers.
Subjects will be assessed for safety, immunogenicity, pharmacokinetics, biomarkers, and
efficacy. No formal interim analyses will be performed.

Prior to enrollment, subjects will undergo screening to determine study eligibility. Upon
enrollment, subjects will receive intravenous (IV) infusions of OMP-18R5 at a assigned
dosing schedule for 56 days. After 56 days, subjects will be assessed for disease status.
If there is no evidence of disease progression or if the tumor is smaller, then subjects may
continue to receive IV infusions of OMP-18R5 every week until disease progression.

Dose escalation will be conducted to determine the maximum tolerated dose (MTD). No dose
escalation or reduction will be allowed within a dose cohort. The first 2 subjects enrolled
in a cohort will not be treated on the same day. The dose may be administered at any time
during the day. Three subjects will be treated at each dose level if no dose-limiting
toxicities (DLTs) are observed. If 1 of 3 subjects experiences a DLT, that dose level will
be expanded to 6 subjects. If 2 or more subjects experience a DLT, no further subjects will
be dosed at that level and 3 additional subjects will be added to the preceding dose cohort
unless 6 subjects have already been treated at that dose level. Subjects will be assessed
for DLTs from the time of the first dose through 28 days. Dose escalation for newly
enrolled subjects, if appropriate, will occur after all subjects in a cohort have completed
their Day 28 DLT assessment. Subjects with stable disease or a response at Day 56 will be
allowed to continue to receive weekly doses of OMP-18R5 until disease progression. An
additional 14 subjects will be enrolled at the highest dose level that result in < 2 of the
6 subjects experiencing a Grade 3 (not including a Grade 3 infusion reaction that resolves
in 24 hours) or 4 adverse event (DLT).

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 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 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 (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 III, or IV (see Appendix D)

10. Subjects with known clinically significant gastrointestinal disease including, but
not limited to, inflammatory bowel disease.

11. Subjects with known osteopenia or osteoporosis.

We found this trial at

sites

University of Michigan Health System

1500 E Medical Center Dr
Ann Arbor, Michigan 48109

(734) 936-4000