A Clinical Trial to Compare the Effectiveness and Safety of RO7771950 in Combination with Trastuzumab and Capecitabine, Versus Tucatinib in Combination with Trastuzumab and Capecitabine, in People with Locally Advanced or Metastatic Breast Cancer that is HER2-Positive

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

8 May 2026 → ongoing

Decision date (initial)

2026-04-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche AG

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety, Pharmacokinetic, Efficacy

To evaluate the efficacy of RO7771950 in combination with trastuzumab and capecitabine (HX) compared with tucatinib in combination with HX with respect to progression-free survival in full analysis set (PFS-FAS)

Secondary objectives 8

1. To evaluate the intracranial efficacy of RO7771950 in combination with HX compared with tucatinib in combination with HX with respect to progression-free survival in participants with CNS metastases (PFS-CNS)
2. To evaluate the efficacy of RO7771950 in combination with HX compared with tucatinib in combination with HX with respect to overall survival in full analysis set (OS-FAS)
3. To evaluate the efficacy of RO7771950 in combination with HX compared with tucatinib in combination with HX in both full analysis safety set and participants with CNS metastases at baseline with respect to objective response rate (ORR), duration of response (DOR) and confirmed benefit rate (CBR)
4. To determine the impact of RO7771950 in combination with HX compared with tucatinib in combination with HX on patient-reported brain tumor-specific symptoms
5. To evaluate patient-reported outcomes (PROs) of functioning and health-related quality of life (HRQoL) associated with RO7771950 in combination with HX compared with tucatinib in combination with HX
6. To evaluate the safety and tolerability of RO7771950 in combination with HX compared with tucatinib in combination with HX
7. To evaluate and compare between treatment arms participants' health utility to generate utility scores for use in economic models for reimbursement
8. To characterize the plasma pharmacokinetic (PK) of RO7771950 and its metabolite(s)

Conditions and MedDRA coding

Pretreated Unresectable Locally Advanced or Metastatic human epidermal growth factor receptor 2 (HER2)-Positive Breast Cancer, with or without Central Nervous System (CNS) Metastases

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

IPD plan description

N/A

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Pathologically documented breast cancer that is locally advanced inoperable (LAI) or metastatic breast cancer (MBC)
2. Confirmed HER2-positive status, as determined according to American Society of Clinical Oncology/College of American Pathologists guidelines, by central laboratory testing of formalin-fixed, paraffin-embedded (FFPE) tumor tissue sample. HER2-positive status will be defined as 3+ by IHC and/or positive by HER2 amplification by in situ hybridization (ISH) with a ratio of ≥ 2 for the number of HER2 gene copies to the number of signals for chromosome 17 copies
3. Stage 1 participants: Measurable disease only, assessable by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and/or Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) Stage 2 participants: Measurable or non-measurable disease assessable by RECIST v1.1 and/or RANO-BM For both stages: Lytic or mixed lytic bone lesions that can be assessed by computed tomography (CT), magnetic resonance imaging (MRI), or X-ray can be accepted as measurable disease in the absence of other measurable lesions.
4. Participants must have received at least one prior line of anti-HER2-based therapy for LAI or metastatic disease
5. Participants must have received prior treatment with an anti-HER2 antibody-drug conjugate (ADC), such as trastuzumab-deruxtecan (T-DXd) or trastuzumab emtansine (T-DM1), administered in the neoadjuvant, adjuvant, or metastatic setting. However, 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.
6. Prior treatment with a tyrosine kinase inhibitor (TKI) in the neoadjuvant/adjuvant setting is acceptable, provided that the interval between the completion of TKI treatment and development of locally advanced inoperable (LAI) or metastatic disease is > 12 months. Prior treatment with TKIs for LAI/metastatic breast cancer (MBC) is not permitted.

Exclusion criteria 5

1. Treatment with investigational therapy within 28 days prior to initiation of study treatment
2. Concurrent anti-cancer treatment. Concurrent use of hormonal therapy for noncancer-related conditions (i.e., hormone replacement therapy for hypothyroidism) or for ovarian function suppression is allowed. Ongoing or planned bisphosphonate treatment is allowed in participants with bone metastases.
3. Based on screening brain MRI, any of the following criteria for participants with brain metastasis: – Progressive neurologic impairment or increased intracranial pressure, which is symptomatic (including nausea, vomiting, blurred vision, headache, epilepsy, etc.) – Any intracranial lesion that is expected to require immediate local therapy. After local therapy, the participant can be re-screened for the protocol. – Requirement for systemic corticosteroids for management of CNS symptoms at a total daily dose of 2 mg of dexamethasone (or equivalent). A stable or tapering dose of 2 mg is permitted. – Requirement for anti-epileptic medication for seizure control, with the exception of stable-dose levetiracetam
4. Participants who meet one of the following cardiac criteria: – Congestive heart failure (CHF; New York Heart Association [NYHA] functional classification) of 2 – Clinically significant peripheral arterial disease, like coronary artery disease, hypertrophic cardiomyopathy, or dilated cardiomyopathy – Abnormalities in the ECG measurements: such as first-degree heart block, second degree heart block, third-degree heart block, prolonged PR interval: 0.20 s – Any clinically significant supraventricular arrhythmia or ventricular arrhythmia requiring treatment or intervention – Unstable angina – Myocardial infarction within the past 6 months – Percutaneous transluminal coronary angioplasty/stenting, coronary artery bypass graft within 6 months of the first dose of the study treatment – QT interval corrected through use of Fridericia's formula (QTcF) prolongation (470 ms for women and 450 ms for men), a known history of QTcF prolongation or Torsade de Pointes; or is on drugs that are required for existing medical conditions and that may result in QT prolongation (e.g., anti-arrhythmic drugs) – Poorly controlled hypertension (e.g., systolic  180 mm Hg or diastolic  100 mmHg) – History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias such as structural heart disease (e.g., severe left ventricular systolic dysfunction [LVSD], left ventricular hypertrophy) – Coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing) – Clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or long QT syndrome
5. Participants with known active and/or untreated hepatitis B or hepatitis C or chronic liver disease are ineligible. Participants with a diagnosis of hepatitis B or C that has been treated and cleared (viral genetic test should fulfil the local laboratory definition for "cleared"), and normal liver function are eligible to participate in the study if the other eligibility parameters are met. Virologic testing should be conducted according to local institutional practices

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-Free Survival in Full Analysis Set (PFS-FAS)

Secondary endpoints 17

1. Progression-Free Survival in participants with CNS metastases (PFS-CNS)
2. Overall Survival in Full Analysis Set (OS-FAS)
3. Objective Response Rate (ORR)
4. Duration Of Response (DOR)
5. Clinical Benefit Rate (CBR)
6. Objective Response Rate in participants with CNS metastases (ORR-CNS)
7. Duration Of Response in participants with CNS metastases (DOR-CNS)
8. Clinical Benefit Rate in participants with CNS metastases (CBR-CNS)
9. Mean and mean changes from baseline score in symptoms experienced by participants with brain tumors, as measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Brain Neoplasm module (EORTC QLQ-BN20)
10. Mean and mean changes from baseline score in function (role, physical, cognitive, social, emotional) and HRQoL by cycle and between treatment arms as measured by the EORTC QLQ-C30
11. Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0)
12. Change from baseline in selected clinical laboratory test results, vital signs, echocardiogram/multiple-gated acquisition (ECHO/MUGA), Electrocardiogram (ECG), and Columbia Suicide Severity Rating Scale (C-SSRS)
13. Presence, frequency of occurrence, severity, and/or degree of interference with daily activities of symptomatic treatment toxicities (i.e., PPE, mouth/throat sores, nausea, vomiting, diarrhea, headache, rash, abdominal pain, decreased appetite, fatigue) as assessed through use of the patient-reported outcome - Common Terminology Criteria for Adverse Events (PRO-CTCAE)
14. 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)
15. Change from baseline/worsening in symptomatic treatment toxicities (PRO-CTCAE) and treatment side-effect bother FACT-GP5
16. Health utility scores of the European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L)
17. Plasma concentration of RO7771950 and its metabolite(s) at specified timepoints

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 6

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation

F. Hoffmann-La Roche AG

Address

Grenzacherstrasse 124

City

Basel

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Third parties 8

Locations

11 EU/EEA countries · 111 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 99 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications