BREnnA: Comparing a new combination treatment with standard treatment to see which works better and is safer for people with HER2-positive advanced breast cancer.A Two-part, Seamless, Multicenter, Randomized, Open-label, Adaptive Phase II/III Study of the Blood-brain Barrier Penetrant RO7771950 Versus Tucatinib, Both in Combination With Trastuzumab and Capecitabine, in Patients With Pretreated Unresectable Locally Advanced or Metastatic HER2-Postivie Breast Cancer, With or Without Central Nervous System Metastases

Inclusion

• Pathologically documented locally advanced inoperable (LAI) or metastatic breast cancer (MBC) with confirmed HER2-positive status by central laboratory
• Measurable disease only as per by RECIST v1.1/RANO-BM in stage 1. Non-measurable disease allowed in stage 2.
• Previously treated (stable or progressive) or previously untreated CNS metastases, or leptomeningeal metastases
• At least one prior line of anti-HER2-based therapy for LAI or metastatic disease
• Prior anti-HER2 antibody-drug conjugate (ADC), such as trastuzumab-deruxtecan (T-DXd) or trastuzumab emtansine (T-DM1), in any treatment setting. Participants for whom prior ADC therapy was not appropriate (e.g., due to lack of access or being medically unfit) may be considered for enrollment.
• Prior tyrosine kinase inhibitor (TKI) in the (neo)adjuvant setting provided completion is > 12 months ahead of LAI occurrence. Prior treatment with TKIs for LAI/MBC is not permitted.
• Has protocol-defined adequate organ and bone marrow function
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Baseline left ventricular ejection fraction (LVEF) >/= 50%