Status:
NOT_YET_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
Lead Sponsor:
Jules Bordet Institute
Collaborating Sponsors:
Hoffmann-La Roche
Conditions:
HER2-positive Metastatic Breast Cancer
HER2-positive Advanced Breast Cancer
Eligibility:
All Genders
18+ years
Phase:
PHASE2
Brief Summary
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 de...
Detailed Description
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 de...
Eligibility Criteria
Inclusion
- ECOG performance status ≤ 1
- Must have histologically or cytologically confirmed progressive advanced/metastatic HER2-positive breast carcinoma as per the updated American Society of Clinical Oncology (ASCO) - College of American Pathologists (CAP) guidelines according to local testing. HER2 status may be determined in the primary breast cancer tumour or, when not available, in a metastatic lesion.
- Multifocal unilateral or bilateral breast adenocarcinoma tumours are allowed if all tested HER2-positive, according to local testing
- Prior treatment with taxane, trastuzumab and pertuzumab (early or advanced setting) and T-DXd (metastatic setting). In order to be eligible, patients subjects must have received T-DXd as the last systemic metastatic treatment line before inclusion, and presented disease progression on this drug.
- Prior therapy with tucatinib, trastuzumab, and capecitabine, in advanced setting, is permissible, provided that T-DXd serves as the last systemic metastatic treatment line before inclusion, and patient subject presented disease progression on this drug.
- Life expectancy ≥ 6 months.
- At screening FDG-PET at least two "target" lesions are required to fulfil the following criteria: (1) anatomically transaxial diameter ≥ 1.5 cm and (2) metabolically assessable with a maximum standard uptake value corrected for lean body mass (SUVmax) ≥ 1.5 x SUVmean + 2 standard deviations (SD) of the liver measured in a 3-cm-diameter spherical volume of interest (VOI) in normal liver parenchyma.
- In case of suspected liver metastasis, a lesion should have a SUVmax ≥ 2 x SUVmean + 3 SD of the blood pool measured in a 1 cm-diameter VOI within descending thoracic aorta. Lesions pre-treated with irradiation are not eligible for consideration as "target" lesions.
- Adequate Bone Marrow Function including:
- Absolute Neutrophil Count (ANC) ≥1000/μL or ≥1x109/L.
- Platelets ≥100,000/μL or ≥ 100 x 109/L.
- Haemoglobin ≥ 9 g/dL.
- Adequate Renal Function including serum creatinine ≤ 1.5 x upper limit of normal (ULN) or estimated creatinine clearance ≥ 60 ml/min as calculated using the method standard for the institution.
- Adequate Liver Function, including all the following parameters:
- Total serum bilirubin ≤ 1.5 x ULN unless the patient subject has documented Gilbert syndrome.
- Aspartate and Alanine Aminotransferase (AST and ALT) ≤ 2.5x ULN.
- Current left ventricular ejection fraction (LVEF) ≥ 50% on echocardiography or multiple-gated acquisition scanning and no history of a LVEF \< 40% or symptomatic heart failure or a recent myocardial infarction.
- Willingness to provide tumour tissue (mandatory biopsy) and blood samples (mandatory) for translational research activities.
- Willingness to comply with the protocol for the duration of the study including treatment and scheduled visits and examinations.
- Signed Informed Consent form (ICF) obtained prior to any study related procedure.
- Inclusion criterion applicable to FRANCE only:
- Affiliated to the French Social Security System
Exclusion
- Prior exposure to T-DM1 for the treatment of metastatic BC. For subjects exposed to T-DM1 for the treatment of early BC, subjects must not have relapsed while on or within 12 months of finishing treatment with T-DM1.
- Brain metastasis as sole metastasis and/or symptomatic or requiring therapy to control symptoms.
- History of interstitial lung disease / pneumonitis (grade 3 or 4) during the prior treatment with T-DXd.
- Cardiopulmonary dysfunction as defined by any of the following:
- Significant symptoms (Grade ≥ 2) relating to LV dysfunction, cardiac arrhythmia, or cardiac ischemia while or since receiving preoperative therapy.
- Uncontrolled hypertension (systolic blood pressure \> 180 mmHg and/or diastolic blood pressure \> 100 mmHg)
- Inadequately controlled angina, serious cardiac arrhythmia not controlled by adequate medication, severe conduction abnormality, or clinically significant valvular disease
- Screening LVEF \< 50% by either ECHO or MUGA
- History of NCI CTCAE (Version 4.0) Grade ≥ 3 symptomatic congestive heart failure (CHF) or New York Heart Association (NYHA) criteria Class ≥ II
- History of a decrease in LVEF to \< 40% or symptomatic CHF with prior trastuzumab treatment (e.g., during preoperative therapy)
- Myocardial infarction within 12 months prior to randomization
- Requirement for continuous oxygen therapy
- Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to trastuzumab or excipients.
- Contra-indication for treatment with T-DM1.
- The number of subjects included in this trial, considered as "rapid progressors" (Rapid progressors defined as progressive disease within the first 6 months of T-DXd therapy) will be capped at 10% at enrolment (no more than 7 subjects out the 78 subjects planned to be recruited). After the first 7 "rapid progressors" included, progression within the first 6 months of T-DXd therapy will be considered as an exclusion criterion.
- Any known liver disease, including known carriers of hepatitis B virus, hepatitis C, autoimmune hepatic disorders and sclerosing cholangitis.
- Concurrent, serious, uncontrolled infections or known infection with HIV. Prior history of other invasive cancer in the past 5 years except basal or squamous cell carcinoma of skin that has been definitively treated.
- Pregnant and/or lactating women, or intending to become pregnant during the study. Serum pregnancy test (for subjects of childbearing potential) positive within 15 days prior to enrolment.
- Women of childbearing potential refusing to use one highly effective method of contraception from ICF signature, during the course of the study and at least 7 months after the last administration of T-DM1.
- Men with childbearing potential partner refusing to use condom during the course of this study and for at least 7 months after the last administration of T-DM1.
- Subject with a significant medical, neuro-psychiatric, or surgical condition, currently uncontrolled by treatment, which, in the principal investigator's opinion, may interfere with completion of the study.
- Exclusion criterion applicable to FRANCE only:
- Vulnerable persons according to the article L.1121-6 of the Public Health Code, adults who are the subject of a measure of legal protection or unable to express their consent according to article L.1121-8 of the Public Health Code.
Key Trial Info
Start Date :
October 1 2025
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
September 1 2029
Estimated Enrollment :
87 Patients enrolled
Trial Details
Trial ID
NCT06595563
Start Date
October 1 2025
End Date
September 1 2029
Last Update
September 3 2025
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