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
165 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
ZEPHIR-02 is a multicentre, open-label phase II study that will enroll subjects with HER2-positive advanced/metastatic breast cancer (mBC) who have experienced disease progression under trastuzumab deruxtecan (T-DXd) in the metastatic setting. All subjects will undergo baseline biopsy, blood collection, FDG-PET/CT and 89Zr-trastuzumab PET/CT (HER2-PET/CT) and will be classified as HER2-PET/CT positive or negative, as previously described in the ZEPHIR trial. Focusing on a central visual "patient-based" classification that captures the entire disease burden, a side-by-side display will be used, comparing baseline FDG-PET/CT (which identifies all FDG-positive metastases regardless of their HER2-imaging status) and HER2-PET/CT. Subjects will be categorized into two HER2-PET/CT patterns (positive vs. negative) based on proportion of FDG-avid tumor load with significant 89Zr-trastuzumab uptake. Subjects classified as "positive" will receive T-DM1 as monotherapy, IV 3.6mg/kg every 3 weeks (21 days +- 3 days) until disease progression, unacceptable toxicity or request of the subject to withdraw from the study. FDG-PET/CT will be performed before cycle 2 of T-DM1 will serve as a research tool to correlate metabolic changes with clinical outcomes. Other FDG-PET/CT will be performed before cycle 4 of T-DM1 for assessment of response. Subjects who demonstrate a partial or complete response (responders) will continue treatment with T-DM1. Subjects who exhibit stable disease or disease progression (non-responders) will discontinue study treatment and enter the survival follow-up period. For responders, subsequent metabolic evaluations will be performed every 3 months, with FDG-PET/CT. Treatment response will be assessed according to metabolic response. For these subjects, mandatory blood samples will be obtained at all metabolic reassessments. Subjects with HER2-PET/CT classified as "negative" will receive treatment of physician's choice (TPC) as per the best local clinical practice and be out of the study. All enrolled subjects will undergo a mandatory biopsy during the pre-treatment period. The study also includes mandatory translational procedures (i.e. collection of tumour biopsy during pre-treatment period and blood samples at pre-specified time points) for exploratory molecular analyses.
CONDITIONS
Official 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 or 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) with progression on T-DXd as last metastatic therapy
- Prior tucatinib, trastuzumab, and capecitabine allowed if T-DXd was last metastatic treatment
- Life expectancy of at least 6 months
- At least two target lesions on FDG-PET meeting specific size and metabolic criteria
- Adequate bone marrow function: ANC ≥ 1000/µL, platelets ≥ 100,000/µL, hemoglobin ≥ 9 g/dL
- Adequate renal function: serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 60 ml/min
- Adequate liver function: total bilirubin ≤ 1.5 x ULN (unless Gilbert syndrome), AST and ALT ≤ 2.5 x ULN
- Left ventricular ejection fraction ≥ 50% with no history of LVEF < 40%, symptomatic heart failure, or recent myocardial infarction
- Willing to provide tumor biopsy and blood samples for research
- Willing to comply with study protocol and visits
- Signed informed consent
- In France only: Affiliated with French Social Security System
You will not qualify if you...
- Prior exposure to T-DM1 for metastatic breast cancer treatment or relapse within 12 months after early breast cancer T-DM1 treatment
- Brain metastasis as sole site or symptomatic requiring therapy
- History of grade 3 or 4 interstitial lung disease or pneumonitis during prior T-DXd treatment
- Significant cardiopulmonary dysfunction including uncontrolled hypertension, severe arrhythmia, low LVEF, symptomatic congestive heart failure, recent myocardial infarction, or need for continuous oxygen
- Known severe hypersensitivity to trastuzumab, T-DM1, or formulation components
- Contraindication to T-DM1 treatment
- Rapid progression within first 6 months of T-DXd therapy exceeding study cap
- Known liver disease including hepatitis B or C, autoimmune hepatic disorders, sclerosing cholangitis
- Serious uncontrolled infections or HIV infection
- Prior invasive cancer within 5 years except certain skin cancers
- Pregnant or lactating women or positive pregnancy test
- Women of childbearing potential not using highly effective contraception during study and 7 months afterward
- Men with partners of childbearing potential not using condoms during study and 7 months afterward
- Significant uncontrolled medical, neuro-psychiatric, or surgical condition affecting study completion
- In France only: Vulnerable persons unable to consent or under legal protection
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 1 location
1
Institut Jules Bordet
Anderlecht, Brussels Capital, Belgium, 1070
Actively Recruiting
Research Team
M
Margot Morelle
CONTACT
I
Ikram El Idrissi
CONTACT
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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