Study of Eribulin Mesylate in Combination With PEGylated Recombinant Human Hyaluronidase (PEGPH20) Versus Eribulin Mesylate Alone in Subjects With Human Epidermal Growth Factor Receptor 2 (HER2)-Negative, High-Hyaluronan (HA) Metastatic Breast Cancer (MBC)

Phase 1b will occur in two parts:

Part 1: Run-in safety cohort(s) (dose levels 1, 0, and -1, as necessary) of 6 participants
each will be conducted until the RP2D is determined. The purpose of the run-in safety
cohort(s) is to study the safety of the 2-drug combination and determine a RP2D. Dose
limiting toxicity (DLT) will be assessed in the first cycle to determine the RP2D of eribulin
mesylate in combination with PEGPH20.

Part 2 (Phase 1b "Expansion Part"): A total of 12 additional participants will be enrolled at
the RP2D determined in Part 1 (using Phase 1b criteria, i.e., participants previously treated
with up to 2 lines of systemic anticancer therapy) in order to assess the safety profile of
the combination and identify any potential safety signals and the incidence of thromboembolic
events in this population.

In Phase 2, participants will be stratified by triple negative breast cancer (TNBC) status
and randomized 1:1 to receive eribulin mesylate and PEGPH20 at the established RP2D level or
eribulin mesylate alone at 1.4 milligrams per square meters (mg/m^2).

Inclusion Criteria

1. Metastatic Her-2- breast cancer

2. Up to 2 prior lines of cytotoxic or targeted anti-cancer therapy for metastatic
disease

3. Measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1

4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1

Exclusion Criteria

1. Less than 6 months since prior neoadjuvant/adjuvant chemotherapy

2. Known central nervous system (CNS) disease, except for those participants with treated
brain metastasis who are stable for at least 1 month, having no evidence of
progression or hemorrhage after treatment and no ongoing requirement for
corticosteroids, as ascertained by clinical examination and brain imaging (MRI or CT)
during the screening period

3. Previous history or current evidence of deep vein thrombosis (DVT), hereditary
thrombophilic syndromes, pulmonary embolism (PE), cerebral vascular accident (CVA),
transient ischemic attack (TIA), atrial fibrillation (AF), or active carotid artery
disease requiring treatment

4. Treatment with chemotherapy, hormonal, or biological therapy within the previous 3
weeks, radiation or small molecule targeted therapy within the previous 2 weeks
preceding informed consent

5. Pregnant or breastfeeding