RO7771950 Versus Tucatinib in Combination With Trastuzumab and Capecitabine in People With Locally Advanced or Metastatic Breast Cancer That is Human Epidermal Growth Factor Receptor 2 (HER2)-Positive (BREnnA)

Roche

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: HER2-positive Breast Cancer

Treatments: Drug: Capecitabine; Drug: Tucatinib; Drug: Trastuzumab; Drug: RO7771950

Study type: Interventional

Funder types: Industry

Identifiers

NCT07413939

2025-524498-17-00 (EU Trial (CTIS) Number)

WO46069

Details and patient eligibility

About

The purpose of this study is to assess the efficacy and safety of RO7771950 in combination with trastuzumab and capecitabine, compared to tucatinib in combination with trastuzumab and capecitabine.

Enrollment: 650 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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650 participants in 3 patient groups

Arm A - RO7771950 Dose Type 1

Experimental group

Treatment:

Drug: Trastuzumab

Drug: RO7771950

Drug: Capecitabine

Arm B - RO7771950 Dose Type 2

Experimental group

Treatment:

Drug: Trastuzumab

Drug: RO7771950

Drug: Capecitabine

Arm C - Tucatinib

Active Comparator group

Treatment:

Drug: Trastuzumab

Drug: Tucatinib

Drug: Capecitabine