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)

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

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.

Study Overview

• Status: Recruiting
• Conditions: HER2-positive Breast Cancer
• Intervention / Treatment: Drug: RO7771950; Drug: Trastuzumab; Drug: Capecitabine; Drug: Tucatinib

• Study Type: Interventional
• Enrollment (Estimated): 650
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: WO46069 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. only); Email: global-roche-genentech-trials@gene.com

Study Locations

• Canada
  • Quebec
    • Québec, Quebec, Canada, G1S 4L8
      • Recruiting
      • Hopital du Saint Sacrement
• Taiwan
  • Taichung, Taiwan, 407219
    • Recruiting
    • Taichung Veterans General Hospital
  • Tainan, Taiwan, 00704
    • Recruiting
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 10041
    • Recruiting
    • National Taiwan Uni Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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%

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A - RO7771950 Dose Type 1	Drug: RO7771950; Participants will receive one of two doses of RO7771950 orally (PO) twice a day (BID).; Other Names: ZN-A-1041; RG6596; Drug: Trastuzumab; Participants will receive trastuzumab in accordance with local prescribing information, either through intravenous (IV) or subcutaneously (SC).; Drug: Capecitabine; Participants will receive capecitabine according to local prescribing information. Capecitabine will be administered PO BID.
Experimental: Arm B - RO7771950 Dose Type 2	Drug: RO7771950; Participants will receive one of two doses of RO7771950 orally (PO) twice a day (BID).; Other Names: ZN-A-1041; RG6596; Drug: Trastuzumab; Participants will receive trastuzumab in accordance with local prescribing information, either through intravenous (IV) or subcutaneously (SC).; Drug: Capecitabine; Participants will receive capecitabine according to local prescribing information. Capecitabine will be administered PO BID.
Active Comparator: Arm C - Tucatinib	Drug: Trastuzumab; Participants will receive trastuzumab in accordance with local prescribing information, either through intravenous (IV) or subcutaneously (SC).; Drug: Capecitabine; Participants will receive capecitabine according to local prescribing information. Capecitabine will be administered PO BID.; Drug: Tucatinib; Participants will receive a dose of tucatinib PO BID.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS) as Determined by Blinded Independent Central Review (BICR)	Time from randomization to disease progression or death, according to standard criteria (Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)/Response Assessment in Neuro-oncology Brain Metastases (RANO-BM)).	Approximately 35 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival in Participants with Central Nervous System Metastases (PFS-CNS) by BICR	Time from randomization to disease progression or death, according to standard criteria (RECIST v1.1/RANO-BM).	Approximately 35 months
Overall Survival in Full Analysis Set (OS-FAS)	Time from randomization to death from any cause.	Approximately 53 months
Objective Response Rate (ORR) by BICR	Proportion of participants with a complete response (CR), partial response (PR) according to standard criteria (RECIST v1.1/RANO-BM).	Approximately 35 months
Duration of Response (DOR) as per BICR	Time from the first occurrence of an objective response (CR or PR) to disease progression or death from any cause according to standard criteria (RECIST v1.1/RANO-BM).	Approximately 35 months
Clinical Benefit Rate (CBR) as per BICR	Proportion of participants with CR, PR, or stable disease (SD) according to standard criteria (RECIST v1.1/RANO-BM).	Approximately 35 months
ORR in Participants with CNS Metastases (ORR-CNS)	Defined as ORR.	Approximately 35 months
DOR in Participants with CNS Metastases (DOR-CNS)	Defined as DOR.	Approximately 35 months
CBR in Participants with CNS Metastases (CBR-CNS)	Defined as CBR.	Approximately 35 months
Changes from Baseline in Symptoms Burden in Participants With Brain Tumors	Measured by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire - Brain Neoplasm module (EORTC QLQ-BN20).	Approximately 35 months
Changes from Baseline in Function and Health-related Quality of Life (HRQoL)	Measured by the EORTC QLQ-Core 30 (C30).	Approximately 35 months
Incidence of Adverse Events (AEs)		Approximately 35 months
Severity of AEs	Severity Determined According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 (v5.0).	Approximately 35 months
Change from Baseline in Echocardiogram (ECHO)/Multiple-gated Acquisition (MUGA)		Approximately 35 months
Change from Baseline in the Columbia-suicide Severity Rating Scale (C-SSRS)		Approximately 35 months
Number of Participants Reporting Presence, Frequency of Occurrence, Severity, and/or Degree of Interference With Daily Activities of Symptomatic Treatment Toxicities as Assessed Through Use of the Patient-reported Outcome (PRO)-CTCAE	Activities can include PPE, Mouth/Throat Sores, Nausea, Vomiting, Diarrhea, Headache, Rash, Abdominal Pain, Decreased Appetite, and Fatigue.	Approximately 35 months
Proportion of Participants Reporting Each Response Option at Each Assessment Timepoint by Treatment Arm for Treatment Side-effect Bother Single-item Functional Assessment of Cancer Therapy (FACT-GP5)		Approximately 35 months
Change from Baseline/Worsening in Symptomatic Treatment Toxicities as Assessed Through Use of the PRO-CTCAE		Approximately 35 months
Change from Baseline/Worsening in Symptomatic Treatment Side-effect Bother FACT-GP5		Approximately 35 months
Health Utility Scores of the European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L)		Approximately 35 months
Plasma Concentration of RO7771950 and its Metabolite(s) at Specified Timepoints		Approximately 35 months

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): September 29, 2032

Study Registration Dates

• First Submitted: February 10, 2026
• First Submitted That Met QC Criteria: February 10, 2026
• First Posted (Actual): February 17, 2026

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 8, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Proteins; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Uracil; Pyrimidinones; Deoxyribonucleosides; Fluorouracil; Trastuzumab; Capecitabine; tucatinib
• Other Study ID Numbers: WO46069; 2025-524498-17-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No