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

Status:	Completed
Conditions:	Cancer
Therapuetic Areas:	Oncology
Healthy:	No
Age Range:	18 - 90
Updated:	5/5/2014
Start Date:	June 2012
End Date:	July 2015

A Phase 1 Dose Escalation Study of OMP-54F28 in Subjects With Solid Tumors

This is an open-label Phase 1 dose escalation study of OMP-54F28 in subjects with a solid
tumor for which there is no remaining standard curative therapy. 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 OMP-54F28 until disease progression. All subjects will
receive Vitamin D3 daily and calcium carbonate twice daily from Day 0 through 30 days
following the discontinuation of OMP-54F28.

Dose escalation will be conducted to determine the maximum tolerated dose (MTD). Subjects
will be dosed at 0.5, 1, 2.5, 5, and 10 mg/kg administered IV once every 3 weeks. No dose
escalation or reduction will be allowed within a dose cohort. Intermediate doses (i.e.,
doses between the dose levels listed above) may also be tested upon agreement with the
investigators and the study sponsor. In addition, alternate dosing schedule cohorts of
OMP-54F28 (eg. every 4 week or every 6 week dosing) can be studied upon agreement with the
investigators and the study sponsor. These alternative less frequent dosing schedules may
be evaluated if emerging data suggest that once every 3 week dosing results in tolerability
concerns. 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 Days 0-28. Dose escalation for
newly enrolled subjects, if appropriate, will occur after all subjects in a cohort have
completed their Day 28 DLT assessment. Subjects who have a >2-fold increase of their
fasting β-CTX or a decline of >3% in their bone mineral density (BMD) from screening or a
T-score decline to <-2.5 in the total femur or L1-L4 DEXA scan measurement will be started
on zoledronic acid. Subjects with stable disease or a response at Day 56 will be allowed to
continue to receive OMP-54F28 until disease progression. An additional 6 subjects will be
enrolled in an expansion cohort at the highest dose level that results in <2 of the 6
subjects experiencing a Grade 3 (not including a Grade 3 infusion reaction that resolves in
24 hours) or Grade 4 adverse event (DLT). Tumors of particular interest for inclusion in
the expansion cohort include sarcomas, basal cell carcinoma, ovarian cancer, desmoid tumors
and prostate cancer given the known importance of the Wnt pathway in these malignancies.

Inclusion Criteria:

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

1. 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.

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. Estimated 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

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:

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

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 or Fc fusion protein

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, Hepatitis B or Hepatitis C 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 osteopenia or osteoporosis on their screening DEXA bone density scan.

12. Subjects with bone metastases that:

1. have a prior history of a pathologic fracture,

2. have a lytic lesion requiring an orthopedic intervention or

3. are not receiving a bisphosphonate zoledronic acid or denosumab as per
institutional guidelines All other subjects with bone metastases are eligible.

13. Subjects receiving a thiazolidinedione PPAR gamma inhibitor; i.e. Actos®
(pioglitazone), Avandia® (rosiglitazone), and Rezulin® (troglitazone).

14. 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.

15. Subjects with a fasting β-CTX of >1000 pg/mL.

16. Subjects with metabolic bone disease, such as hyperparathyroidism, Paget's disease or
osteomalacia.

17. Subjects with a history of or a newly diagnosed insufficiency fracture or
morphometric (asymptomatic) vertebral fracture on the screening lateral lumbosacral
spine film.

We found this trial at

sites

Pinnacle Oncology Hematology

Scottsdale, Arizona 85258

from

Scottsdale, AZ