MM-302 Plus Trastuzumab vs. Chemotherapy of Physician's Choice Plus Trastuzumab in HER2-Positive Locally Advanced/Metastatic Breast Cancer Patients

Inclusion Criteria:

- Patients must have histologically or cytologically confirmed invasive cancer of the
breast

- Patients must have documented locally advanced/metastatic disease, defined by the
investigator, which is not amenable to resection with curative intent.

- Patients must have HER2-positive breast cancer as defined by ASCO/CAP 2013 guidelines
that is confirmed by a Sponsor-designated central laboratory

- Patients must have progressed on, or be intolerant to pertuzumab in the LABC/MBC
setting or had disease recurrence within 12 months of pertuzumab treatment in the
neoadjuvant or adjuvant setting.

- Patients must have progressed on, or be intolerant to ado-trastuzumab emtansine in
the LABC/MBC setting

- Patients must have been previously treated with trastuzumab in any setting (which may
have been previously administered with or without pertuzumab)

- ECOG Performance Status of 0 or 1

Exclusion Criteria:

- Patients who have previously been treated with doxorubicin, liposomal doxorubicin,
epirubicin, mitoxantrone, or any other anthracycline derivative

- Subjects with central nervous system (CNS) metastases, unless they have been treated
and are stable without symptoms for 4 weeks after completion of treatment and must be
off steroids for at least 4 weeks prior to enrollment

- Patients with any class of New York Heart Association (NYHA) CHF or heart failure
with preserved ejection fraction (HFPEF)

- Patients with a history of known coronary artery disease or a myocardial infarction
within the last 12 months

- Patients with a known history of serious cardiac arrhythmias requiring treatment
(exception: controlled atrial fibrillation, paroxysmal supraventricular tachycardia)

- Patients who previously discontinued trastuzumab due to unacceptable cardiac toxicity

- Patients with a history of LVEF decline to below 50% during or after prior
trastuzumab/lapatinib or other HER2 directed therapy.