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
This is not medical advice. AI-assisted translation — inaccuracies may occur. Always verify the original and consult your oncologist before taking any steps.
About the trial
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.
Original English text from ClinicalTrials.gov
Who can (and can't) join
✓ Qualifies
- •Pacjentki z zaawansowanym lub rozsianym rakiem piersi, który jest HER2-dodatni.
- •Rak piersi musi wykazywać cechy HER2-dodatnie według aktualnych wytycznych.
- •Choroba musi postępować pomimo leczenia lekiem trastuzumab deruxtecan (T-DXd).
- •Pacjentki wcześniej przyjmowały leki: taksan, trastuzumab, pertuzumab oraz T-DXd.
- •Stan ogólny pacjentki pozwala na udział w badaniu ( ECOG ≤ 1).
- •Przewidywana długość życia co najmniej 6 miesięcy.
- •Obecność co najmniej dwóch widocznych zmian nowotworowych do oceny.
- •Odpowiednia liczba krwinek i hemoglobiny we krwi.
✗ Disqualifies
- •Choroba rak piersi, która nie jest HER2-dodatnia.
- •Rak piersi, który nie wykazywał progresji po leczeniu T-DXd.
- •Stan ogólny pacjentki uniemożliwiający udział w badaniu (np. słabsza kondycja niż ECOG ≤ 1).
- •Przeszłe leczenie promieniami zmian wymagających oceny w badaniu.
- •Poważne choroby innych narządów (np. serca, płuc, wątroby, nerek) mogą wykluczać udział.
- •Ciąża lub karmienie piersią.
Simplified criteria — AI translation
Trial details
- Minimum age
- 18 Years
- Last updated (source)
- July 2, 2026
- Sex
- No restrictions
Therapies / drugs in trial
Locations (8)
Institut Jules Bordet
Anderlecht, Belgium
CHU Charleroi - Marie Curie
Charleroi, Belgium
UZ Gent
Ghent, Belgium
UZ Leuven
Leuven, Belgium
CHU Liège
Liège, Belgium
AZ Delta
Roeselare, Belgium
VUMC Amsterdam
Amsterdam, Netherlands
UMC Groeningen
Groningen, Netherlands
Trial contact
Margot Morelle
Ikram El Idrissi
Contact information from ClinicalTrials.gov. Contact in English.
Data from ClinicalTrials.gov. AI-assisted translation, last sync: 7/1/2026.