Actively Recruiting
HER2 Molecular Imaging With 89Zr-trastuzumab PET/CT as a Predictive Biomarker for Antibody-drug Conjugate Sequencing in Patients With Advanced HER2-positive Breast Cancer
Led by Jules Bordet Institute · Updated on 2026-05-07
87
Participants Needed
1
Research Sites
78 weeks
Total Duration
On this page
Sponsors
J
Jules Bordet Institute
Lead Sponsor
H
Hoffmann-La Roche
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are investigating HER2 molecular imaging using 89Zr-trastuzumab PET/CT as a predictive biomarker for treatment sequencing in patients with advanced HER2-positive breast cancer who have progressed after trastuzumab deruxtecan (T-DXd). This phase II, multicenter, open-label study aims to classify patients based on HER2-PET/CT imaging patterns to guide subsequent therapy choices. Participants will undergo baseline biopsy, blood sampling, FDG-PET/CT, and 89Zr-trastuzumab PET/CT scans. Those classified as HER2-PET/CT positive will receive trastuzumab emtansine (T-DM1) intravenously at 3.6 mg/kg every three weeks until disease progression, unacceptable toxicity, or withdrawal. FDG-PET/CT scans will assess early treatment response before cycles 2 and 4. Responders continue T-DM1 with metabolic evaluations every three months, while non-responders stop treatment and enter survival follow-up. Patients classified as HER2-PET/CT negative will receive physician's choice treatment and enter survival follow-up. Throughout the study, participants will provide mandatory biopsies and blood samples for molecular analyses. Researchers will monitor genomic changes and HER2 expression up to two years and evaluate time to treatment failure and overall survival during treatment. Safety and disease control rates under T-DM1 will also be assessed. The total study duration includes treatment, follow-up, and translational research activities.
CONDITIONS
Brief Title
HER2 Molecular Imaging With 89Zr-trastuzumab PET/CT as a Predictive Biomarker for Antibody-drug Conjugate Sequencing in Patients With Advanced HER2-positive Breast Cancer
Who Can Participate
Eligibility Criteria
You may qualify if you...
- ECOG performance status 0 or 1
- Histologically or cytologically confirmed progressive advanced/metastatic HER2-positive breast cancer
- Multifocal unilateral or bilateral breast adenocarcinoma allowed if all tumors are HER2-positive
- Prior treatment with taxane, trastuzumab, pertuzumab, and trastuzumab deruxtecan (T-DXd) in metastatic setting with disease progression on T-DXd
- Prior therapy with tucatinib, trastuzumab, and capecitabine permitted if T-DXd was the last metastatic treatment
- Life expectancy of at least 6 months
- At least two target lesions on FDG-PET meeting size and metabolic activity criteria
- Adequate bone marrow, renal, and liver function
- Left ventricular ejection fraction (LVEF) of 50% or higher with no history of severe heart failure
- Willingness to provide mandatory biopsy and blood samples
- Willingness to comply with study protocol and scheduled visits
- Signed informed consent form
- Affiliation to French Social Security System (France only)
You will not qualify if you...
- Prior exposure to T-DM1 for metastatic breast cancer or relapse within 12 months if treated for early breast cancer
- Brain metastasis as sole metastasis or symptomatic requiring treatment
- History of grade 3 or 4 interstitial lung disease or pneumonitis during prior T-DXd treatment
- Significant cardiopulmonary dysfunction or uncontrolled hypertension
- LVEF below 50% or history of symptomatic heart failure
- Myocardial infarction within 12 months prior to enrollment
- Continuous oxygen therapy requirement
- Severe hypersensitivity to trastuzumab or study drug components
- Contraindications for T-DM1 treatment
- Rapid progressors exceeding 10% of enrollment
- Known liver diseases including hepatitis B or C, autoimmune hepatic disorders
- Serious uncontrolled infections or HIV infection
- Recent invasive cancer except treated skin cancer
- Pregnant or lactating women or those unwilling to use effective contraception
- Significant uncontrolled medical, neuro-psychiatric, or surgical conditions
- Vulnerable persons unable to consent (France only)
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to 1 week
Participants undergo mandatory biopsy, blood collection, FDG-PET/CT, and 89Zr-trastuzumab PET/CT to classify HER2-PET/CT status and inform treatment.
1 to 2 visits
Duration - Up to 1 year
Participants classified as HER2-PET/CT positive receive T-DM1 intravenous infusions every 3 weeks until disease progression, unacceptable toxicity, or withdrawal. Early FDG-PET/CT assessments occur before cycles 2 and 4 to evaluate response. Responders continue treatment with metabolic evaluations and blood sampling every 3 months.
Infusions every 3 weeks; FDG-PET/CT before cycles 2 and 4; metabolic assessments every 3 months for responders
Duration - Varies based on treatment
Participants classified as HER2-PET/CT negative receive treatment of physician's choice according to local clinical practice and enter survival follow-up.
Visit schedule according to physician's choice
Duration - Up to 2 years
Participants who discontinue treatment or receive non-T-DM1 therapy are followed to monitor survival outcomes.
Periodic visits as per study protocol
Trial Site Locations
Total: 1 location
1
Institut Jules Bordet
Anderlecht, Brussels Capital, Belgium, 1070
Actively Recruiting
Research Team
M
Margot Morelle
I
Ikram El Idrissi
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
2
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