HER2-positive Breast Cancer
Conditions
Brief summary
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.
Interventions
DRUGRO7771950
Participants will receive one of two doses of RO7771950 orally (PO) twice a day (BID).
DRUGTucatinib
Participants will receive a dose of tucatinib PO BID.
DRUGTrastuzumab
Participants will receive trastuzumab in accordance with local prescribing information, either through intravenous (IV) or subcutaneously (SC).
DRUGCapecitabine
Participants will receive capecitabine according to local prescribing information. Capecitabine will be administered PO BID.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) as Determined by Blinded Independent Central Review (BICR) | Approximately 35 months | Time from randomization to disease progression or death, according to standard criteria (Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival in Participants with Central Nervous System Metastases (PFS-CNS) by BICR | Approximately 35 months | Time from randomization to disease progression or death, according to standard criteria (RECIST v1.1). |
| Overall Survival in Full Analysis Set (OS-FAS) | Approximately 53 months | Time from randomization to death from any cause. |
| Objective Response Rate (ORR) by BICR | Approximately 35 months | Proportion of participants with a complete response (CR), partial response (PR) according to standard criteria (RECIST v1.1). |
| Duration of Response (DOR) as per BICR | Approximately 35 months | 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). |
| Clinical Benefit Rate (CBR) as per BICR | Approximately 35 months | Proportion of participants with CR, PR, or stable disease (SD) according to standard criteria (RECIST v1.1). |
| ORR in Participants with CNS Metastases (ORR-CNS) | Approximately 35 months | Defined as ORR. |
| DOR in Participants with CNS Metastases (DOR-CNS) | Approximately 35 months | Defined as DOR. |
| CBR in Participants with CNS Metastases (CBR-CNS) | Approximately 35 months | Defined as CBR. |
| Changes from Baseline in Symptoms Burden in Participants With Brain Tumors | Approximately 35 months | Measured by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire - Brain Neoplasm module (EORTC QLQ-BN20). |
| Changes from Baseline in Function and Health-related Quality of Life (HRQoL) | Approximately 35 months | Measured by the EORTC QLQ-Core 30 (C30). |
| Incidence of Adverse Events (AEs) | Approximately 35 months | — |
| Severity of AEs | Approximately 35 months | Severity Determined According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 (v5.0). |
| 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 | Approximately 35 months | Activities can include PPE, Mouth/Throat Sores, Nausea, Vomiting, Diarrhea, Headache, Rash, Abdominal Pain, Decreased Appetite, and Fatigue. |
| 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 | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Czechia, France, Germany, Hungary, Israel, Italy, New Zealand, Poland, Portugal, South Africa, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTReference Study ID Number: WO46069 https://forpatients.roche.com/ No attachments to email below.
CONTACTFastest response: use the inquiry form. https://www.gene.com/contact-us/submit-medical-inquiry
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Outcome results
None listed