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.