This study is a Phase 1 and pharmacologic open-label dose-escalation trial using a "3+3" design. Successive cohorts of three or more patients will be treated at escalating doses until a maximum tolerated dose is identified. Once the maximum tolerated dose is identified, an Expansion Cohort will be enrolled at that dose to further characterize safety and pharmacologic endpoints. Additional arms will be enrolled to explore the combination of MM-302 with trastuzumab or trastuzumab plus cyclophosphamide in patients with advanced HER2 positive breast cancer.

Inclusion Criteria:

• Locally advanced/unresectable or metastatic breast cancer
• Eighteen years of age or above
• Able to understand and sign an informed consent (or have a legal representative who is able to do so)
• Measurable disease according to RECIST v1.1
• ECOG Performance Score of 0 or 1
• Adequate bone marrow, hepatic, renal and cardiac function
• Willing to abstain from sexual intercourse or to use an effective form of contraception during the study and for 90 days following the last dose of MM-302

Exclusion Criteria:

• Patients for whom potentially curative anticancer therapy is available
• Active infection or fever > 38.5°C during screening visits or on the first scheduled day of dosing
• Symptomatic CNS disease
• Known hypersensitivity to any of the components of MM-302 or who have had hypersensitivity reactions to fully human monoclonal antibodies
• Received other recent antitumor therapy
• Pregnant or breast feeding
• Patients with any other medical or psychological condition, deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results