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

Phase 3Not Yet RecruitingNCT07413939

Hoffmann-La Roche650 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

650

Conditions

HER2-positive Breast Cancer

Interventions

RO7771950DRUG

Participants will receive one of two doses of RO7771950 orally (PO) twice a day (BID).

TucatinibDRUG

Participants will receive a dose of tucatinib PO BID.

TrastuzumabDRUG

Participants will receive trastuzumab in accordance with local prescribing information, either through intravenous (IV) or subcutaneously (SC).

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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)).