• Have confirmed HER2+ breast cancer, as defined by the current American Society of Clinical Oncology - College of American Pathologists (ASCO/CAP) guidelines, previously determined at a Clinical Laboratory Improvements Amendments (CLIA)-certified or International Organization for Standardization (ISO)-accredited laboratory.

• History of prior treatment with a taxane and trastuzumab in the LA/M setting OR progressed within 6 months after neoadjuvant or adjuvant treatment, including a taxane and trastuzumab.

• Have progression of unresectable LA/M breast cancer after last systemic therapy (as confirmed by investigator), or be intolerant of last systemic therapy

• Have measurable disease assessable by RECIST v1.1

• Have Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1

• Have a life expectancy of at least 6 months, in the opinion of the investigator

• CNS Inclusion - Based on medical history and screening contrast brain magnetic resonance imaging (MRI), participants with a history of brain metastases must have one of the following:

‣ Untreated brain metastases not needing immediate local therapy. For participants with untreated central nervous system (CNS) lesions \>2.0 cm on screening contrast brain MRI, discussion with and approval from the medical monitor is required prior to enrollment

⁃ Previously treated brain metastases

• Brain metastases previously treated with local therapy may either be stable since treatment or may have progressed since prior local CNS therapy, provided that there is no clinical indication for immediate re-treatment with local therapy in the opinion of the investigator

∙ Participants treated with CNS local therapy for newly identified or previously treated progressing lesions found on contrast brain MRI performed during screening for this study may be eligible to enroll if all of the following criteria are met:

‣ Time since whole brain radiation therapy (WBRT) is ≥14 days prior to first dose of study treatment, time since stereotactic radiosurgery (SRS) is ≥7 days prior to first dose of study treatment, or time since surgical resection is ≥28 days

⁃ Other sites of measurable disease by RECIST v1.1 are present

∙ Relevant records of any CNS treatment must be available