A Phase 1b Study of T-DXd Combinations in HER2-low Advanced or Metastatic Breast Cancer

Key Inclusion Criteria: * Patients must be at least 18 years of age * Male or female patients who have pathologically documented breast cancer that: 1. Has a history of HER2-low expression, defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested) with a validated assay 2. Is documented as HR+ (either ER and/or PgR positive \[ER or PgR ≥1%\]) or ER and PgR negative (ER and PgR \<1%) per ASCO/CAP guidelines in the metastatic setting * Patient must have adequate tumor sample for biomarker assessment * ECOG Performance Status of 0 or 1 For patients with HR+ disease: Part 1: At least 1 prior treatment line of ET with or without a targeted therapy (such as CDK4/6, mTOR or PI3-K inhibitors), and at least 1 prior line of chemotherapy for MBC are required. Part 2: Only 1 prior treatment line of ET with or without a targeted therapy (such as CDK4/6, mTOR or PI3-K inhibitors) for MBC is allowed. No prior chemotherapy in the metastatic setting is allowed. Note there are no patients with HR+ disease in Part 2 of Modules 2 and 3. For patients with HR- disease: Part 1: At least 1 prior line of chemotherapy for MBC is required. Note there are no patients with HR- disease in Part 1 of Modules 4 and 5. Part 2: For Module 2, no prior lines of therapy for MBC are allowed, and for Modules 1 and 3, only 1 prior line of chemotherapy for MBC is allowed. Note there are no patients with HR- disease in Part 2 of Modules 4 and 5. Key Exclusion Criteria: * Uncontrolled intercurrent illness * Uncontrolled or siginificant cardiovascular disease * History of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening. * Lung-specific intercurrent clinically significant illnesses * Has spinal cord compression or clinically active central nervous system metastases * Active primary immunodeficiency * Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals * Prior treatment with ADC that comprises of an exatecan derivative that is a topoisomerase I inhibitor.