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

Exclusion Criteria

• •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
• •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.