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

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.
Brief Title
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
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
888-662-6728 (U.S. only)
Central Contact Email
global-roche-genentech-trials@gene.com
Central Contact Role
Contact
Completion Date
Completion Date Type
Estimated
Conditions
HER2-POSITIVE BREAST CANCER
Eligibility Criteria
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.
Inclusion Criteria
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%.

Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT07413939
Org Class
Industry
Org Full Name
Hoffmann-La Roche
Org Study Id
WO46069
Overall Status
Recruiting
Phases
Phase 2
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
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-Positive Breast Cancer, With or Without Central Nervous System Metastases
Primary Outcomes
Outcome Description
Time from randomization to disease progression or death, according to standard criteria (Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)).
Outcome Measure
Progression-free Survival (PFS) as Determined by Blinded Independent Central Review (BICR)
Outcome Time Frame
Approximately 35 months
Secondary Ids
Secondary Id
2025-524498-17-00
Secondary Id
2025
Secondary Outcomes
Outcome Description
Time from randomization to disease progression or death, according to standard criteria (RECIST v1.1).
Outcome Time Frame
Approximately 35 months
Outcome Measure
Progression-free Survival in Participants with Central Nervous System Metastases (PFS-CNS) by BICR
Outcome Description
Time from randomization to death from any cause.
Outcome Time Frame
Approximately 53 months
Outcome Measure
Overall Survival in Full Analysis Set (OS-FAS)
Outcome Description
Proportion of participants with a complete response (CR), partial response (PR) according to standard criteria (RECIST v1.1).
Outcome Time Frame
Approximately 35 months
Outcome Measure
Objective Response Rate (ORR) by BICR
Outcome Description
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).
Outcome Time Frame
Approximately 35 months
Outcome Measure
Duration of Response (DOR) as per BICR
Outcome Description
Proportion of participants with CR, PR, or stable disease (SD) according to standard criteria (RECIST v1.1).
Outcome Time Frame
Approximately 35 months
Outcome Measure
Clinical Benefit Rate (CBR) as per BICR
Outcome Description
Defined as ORR.
Outcome Time Frame
Approximately 35 months
Outcome Measure
ORR in Participants with CNS Metastases (ORR-CNS)
Outcome Description
Defined as DOR.
Outcome Time Frame
Approximately 35 months
Outcome Measure
DOR in Participants with CNS Metastases (DOR-CNS)
Outcome Description
Defined as CBR.
Outcome Time Frame
Approximately 35 months
Outcome Measure
CBR in Participants with CNS Metastases (CBR-CNS)
Outcome Description
Measured by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire - Brain Neoplasm module (EORTC QLQ-BN20).
Outcome Time Frame
Approximately 35 months
Outcome Measure
Changes from Baseline in Symptoms Burden in Participants With Brain Tumors
Outcome Description
Measured by the EORTC QLQ-Core 30 (C30).
Outcome Time Frame
Approximately 35 months
Outcome Measure
Changes from Baseline in Function and Health-related Quality of Life (HRQoL)
Outcome Time Frame
Approximately 35 months
Outcome Measure
Incidence of Adverse Events (AEs)
Outcome Description
Severity Determined According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 (v5.0).
Outcome Time Frame
Approximately 35 months
Outcome Measure
Severity of AEs
Outcome Time Frame
Approximately 35 months
Outcome Measure
Change from Baseline in Echocardiogram (ECHO)/Multiple-gated Acquisition (MUGA)
Outcome Time Frame
Approximately 35 months
Outcome Measure
Change from Baseline in the Columbia-suicide Severity Rating Scale (C-SSRS)
Outcome Description
Activities can include PPE, Mouth/Throat Sores, Nausea, Vomiting, Diarrhea, Headache, Rash, Abdominal Pain, Decreased Appetite, and Fatigue.
Outcome Time Frame
Approximately 35 months
Outcome Measure
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
Outcome Time Frame
Approximately 35 months
Outcome Measure
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)
Outcome Time Frame
Approximately 35 months
Outcome Measure
Change from Baseline/Worsening in Symptomatic Treatment Toxicities as Assessed Through Use of the PRO-CTCAE
Outcome Time Frame
Approximately 35 months
Outcome Measure
Change from Baseline/Worsening in Symptomatic Treatment Side-effect Bother FACT-GP5
Outcome Time Frame
Approximately 35 months
Outcome Measure
Health Utility Scores of the European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L)
Outcome Time Frame
Approximately 35 months
Outcome Measure
Plasma Concentration of RO7771950 and its Metabolite(s) at Specified Timepoints
Start Date
Start Date Type
Actual
Status Verified Date
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Della Makower
Investigator Email
DMAKOWER@montefiore.org
Investigator Department
Medicine
Investigator Division
Oncology
Investigator Sponsor Organization
External
Study Department
Oncology (Medical/Hematologic)
Study Division
Medical and Hematologic Oncology
MeSH Terms
TUCATINIB
TRASTUZUMAB
CAPECITABINE
ANTIBODIES, MONOCLONAL, HUMANIZED
ANTIBODIES, MONOCLONAL
ANTIBODIES
IMMUNOGLOBULINS
IMMUNOPROTEINS
BLOOD PROTEINS
PROTEINS
AMINO ACIDS, PEPTIDES, AND PROTEINS
SERUM GLOBULINS
GLOBULINS
DEOXYCYTIDINE
CYTIDINE
PYRIMIDINE NUCLEOSIDES
PYRIMIDINES
HETEROCYCLIC COMPOUNDS, 1-RING
HETEROCYCLIC COMPOUNDS
FLUOROURACIL
URACIL
PYRIMIDINONES
DEOXYRIBONUCLEOSIDES
NUCLEOSIDES
NUCLEIC ACIDS, NUCLEOTIDES, AND NUCLEOSIDES