RO7771950 versus tucatinib with trastuzumab and capecitabine for HER2-positive locally advanced or metastatic breast cancer
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
This test will see if RO7771950 combined with trastuzumab and capecitabine works better than tucatinib combined with the same drugs for people with HER2-positive locally advanced or metastatic breast cancer.
Quick facts
| Phase | Phase2; Phase3 |
|---|---|
| Study type | Interventional |
| Enrollment | 650 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Hoffmann-La Roche Industry-sponsored |
| Drugs / interventions | trastuzumab, tucatinib |
| Locations | 4 sites (Québec, Quebec and 3 other locations) |
| Trial ID | NCT07413939 on ClinicalTrials.gov |
What this trial studies
This phase 2/3 randomized trial compares RO7771950 plus trastuzumab and capecitabine against tucatinib plus trastuzumab and capecitabine in adults with centrally confirmed HER2-positive locally advanced inoperable or metastatic breast cancer. Participants are randomized to one of the two combination regimens and treated until disease progression or unacceptable toxicity. Key eligibility includes at least one prior line of anti-HER2 therapy for advanced disease, allowance for prior antibody-drug conjugate exposure, and protocol-defined inclusion of patients with CNS or leptomeningeal metastases. Primary outcomes include tumor response, progression-free and overall survival, and safety/tolerability.
Who should consider this trial
Good fit: Ideal candidates are adults with centrally confirmed HER2-positive locally advanced inoperable or metastatic breast cancer who have received at least one prior anti-HER2 therapy for advanced disease and meet the trial's organ function and disease measurability requirements.
Not a fit: Patients who previously received a tyrosine kinase inhibitor for their advanced disease (within disallowed windows), who have inadequate organ function, are pregnant, or cannot attend study visits are unlikely to be eligible or to benefit from participation.
Why it matters
Potential benefit: If successful, the RO7771950 combination could offer a more effective or better-tolerated treatment option for people with HER2-positive advanced breast cancer, including those with brain metastases.
How similar studies have performed: Tucatinib combined with trastuzumab and capecitabine has shown benefit in prior trials, particularly for patients with brain metastases, while RO7771950 is an investigational agent with limited prior clinical data.
Eligibility criteria
Show full inclusion / exclusion criteria
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
Where this trial is running
Québec, Quebec and 3 other locations
- Hopital du Saint Sacrement — Québec, Quebec, Canada (Recruiting)
- Taichung Veterans General Hospital — Taichung, Taiwan (Recruiting)
- National Cheng Kung University Hospital — Tainan, Taiwan (Recruiting)
- National Taiwan Uni Hospital — Taipei, Taiwan (Recruiting)
Study contacts
- Study coordinator: Reference Study ID Number: WO46069 https://forpatients.roche.com/
- Email: global-roche-genentech-trials@gene.com
- Phone: 888-662-6728 (U.S. only)
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.