Dose Escalation Study of OMP-54F28 in Combination With Paclitaxel and Carboplatin in Patients With Recurrent Platinum-Sensitive Ovarian Cancer

Depending on safety in this study, additional lower or intermediate dose levels may be
evaluated. Depending on emerging safety data from the Phase 1a study 54F28-001 with
continuing dose escalation, additional higher dose levels of OMP-54F28 may be evaluated in
this study. Alternative dosing schedules of OMP-54F28 may be explored based on emerging
nonclinical and clinical data for safety, PD, PK and efficacy. The starting dose for a new
dosing schedule will be chosen to result in an AUC equivalent to the highest dose level that
cleared on the previously studied dosing schedule. No dose escalation of OMP-54F28 will be
allowed within a dose cohort.

Once the maximum tolerated dose (MTD) or maximum administered dose (MAD) has been determined,
up to 10 patients may be enrolled in the cohort-expansion phase to better characterize the
safety, tolerability and PK of OMP-54F28 combined with paclitaxel and carboplatin. Up to
approximately 34 patients may be enrolled into the study.

Inclusion Criteria:

- Signed Informed Consent Form

- Age ≥18 years

- Histologically documented ovarian, primary peritoneal or fallopian tube cancer

- Recurrent platinum-sensitive disease, defined as disease progression ≥6 months after
completing a minimum of 4 cycles of a platinum-containing regimen

- Availability of FFPE tumor tissue, either archival or obtained at study entry through
fresh biopsy

o Tumor tissue from fine needle aspiration is not acceptable.

- ECOG performance status of 0 or 1

- All acute treatment-related toxicity from prior therapy must have resolved to Grade ≤
1 prior to study entry

- Adequate hematologic and end-organ function

- Evaluable or measurable disease per RECIST v1.1

- For women of childbearing potential, agreement to use two effective forms of
contraception

Exclusion Criteria:

- Non-epithelial ovarian carcinoma, including malignant mixed Mullerian tumors

- Prior treatment with paclitaxel and carboplatin for recurrent platinum-sensitive
ovarian cancer

- Treatment with any anti-cancer therapy, including radiotherapy, chemotherapy, biologic
therapy, or herbal therapy within 3 weeks or 5 half-lives (for systemic agents),
whichever is shorter

- Known hypersensitivity to any component of study treatments that resulted in drug
discontinuation

- Grade ≥ 2 sensory neuropathy

- Uncontrolled seizure disorder or active neurologic disease

- Untreated brain metastases

- Leptomeningeal disease as a manifestation of cancer

- Active infection requiring antibiotics

- Bisphosphonate therapy for symptomatic hypercalcemia

- Known history of clinically significant liver disease, including active viral
hepatitis and cirrhosis

- Significant intercurrent illness including, but not limited to, unstable angina
pectoris, and cardiac arrhythmia, or psychiatric illness/social situation that would
limit compliance with study requirements

- Pregnancy, lactation, or breastfeeding

- Known HIV infection

- Evidence of bleeding diathesis or significant coagulopathy (in the absence of
therapeutic anticoagulation)

- Concurrent use of therapeutic warfarin

- New York Heart Association Classification III or IV

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

- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to the first dose of study treatment or anticipation of need for major surgical
procedure during the course of the study

- Osteoporosis based on a T-score of <-2.5 at the left or right total hip, left or right
femoral neck or lumbar spine (L1-L4) as determined by DEXA scan

- Bone metastases and one of the following:

- Prior history of a pathologic fracture

- Lytic lesion requiring an impending orthopedic intervention

- Lack of treatment with a bisphosphonate or denosumab

- Treatment with a thiazolidinedione PPAR gamma inhibitor; e.g. Actos® (pioglitazone)
and Avandia® (rosiglitzone)

- Active treatment with an oral or IV glucocortocoid for ≥4 weeks at a daily dose
equivalent to or greater than 7.5 mg of oral prednisone

- Fasting β-CTX of >1000 pg/mL

- Metabolic bone disease, such as hyperparathyroidism, Paget's disease or osteomalacia