Phase 3 study for people with Breast Cancer

Reproduced exactly, unedited. Written for researchers rather than for patients.

Inclusion Criteria:

• Pathologically documented locally advanced inoperable (LAI) or metastatic breast cancer (MBC) with confirmed HER2-positive status by central laboratory.
• Measurable disease as per by RECIST v1.1 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 without prior ADC therapy may only be enrolled if approved standard-of-care (SOC) anti-HER2 ADC is not locally accessible at screening, or if there is a prospectively documented clinical contraindication.
• 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%.

Exclusion Criteria:

• Concurrent anti-cancer treatment, or treatment with investigational therapy within 28 days prior to initiation of study treatment.
• Known active/untreated hepatitis B or C or chronic liver disease.
• Clinically significant cardiovascular disease or risk, including heart failure (New York Heart Association (NYHA) ≥ II), ischemic heart disease or recent coronary events/interventions, clinically significant arrhythmias or electrocardiogram (ECG) abnormalities, QT prolongation or risk of ventricular dysrhythmias, poorly controlled hypertension, peripheral arterial disease, dilated cardiomyopathy, or unstable angina.
• Clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or long QT syndrome.
• Concomitant use of any drug or herbal medicine known to strongly inhibit or induce CYP3A4 or CYP2C8 activity, oral coumarin-derivative anticoagulants.