A Study of Tucatinib Plus Trastuzumab Deruxtecan in HER2+ Breast Cancer

Inclusion Criteria * 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 h…