Patient-Centered Study of Trastuzumab Deruxtecan (T-DXd) in First-Line HER2-Positive Metastatic Breast Cancer With Proactive Toxicity Management Reflecting Real-World Clinical Practice
This is an open-label, single arm, non-randomized, multicenter, phase 2 study assessing the efficacy and safety of T-DXd as first-line treatment in HER2-positive advanced/metastatic BC patients (N=300). The study integrates digital health tools for proactive toxicity management and potentially facilitate early detection of ILD/pneumonitis.
• Able to understand the nature of the study and to voluntarily provide written informed consent prior to any trial-specific screening procedures and has sufficient cognitive capacity to comply with study requirements, including the use of digital health tools and devices.
• Male/female patients who are at least 18 years of age on the day of signing informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Histologically or cytologically locally confirmed HR+/HER2+ or HR-/HER2+ BC with evidence of locally advanced disease, not amenable to resection or radiation therapy with curative intent, or metastatic disease:
∙ HER2-positivity confirmed in a tumor sample obtained in the metastatic setting, defined as either IHC 3+ or in situ hybridization positive (ISH+) by local laboratory assessment as per the most recent American Society of Clinical Oncology (ASCO)-College of American Pathologists Guideline (CAP) guideline. The most recent test result prior screening period will be used to confirm eligibility.
‣ Documented HR (ER and/or PR) positivity or negativity, confirmed by local laboratory assessment in a tumor sample obtained in the metastatic setting. ER and/or PR positivity is defined as \>1% of cells expressing HR via IHC analysis as per most recent ASCO-CAP guideline. The most recent test result prior screening period will be used to confirm eligibility.
• No prior chemotherapy or HER2-targeted therapy for advanced or mBC (1 prior line of endocrine therapy is allowed for mBC). Participants who have received chemotherapy or HER2-targeted therapy in the neoadjuvant or adjuvant setting at any time are eligible.
• Note: Patients that received an antibody-drug conjugate containing an exatecan derivative (topoisomerase I inhibitor) in the adjuvant setting, must have a disease-free interval of ≥12 months since the last dose.
• Evaluable disease as defined by RECIST v1.1.
• Note: Previously irradiated lesions can be considered as measurable disease only if disease progression has been unequivocally documented at that site since radiation.
• Adequate FFPE tumor tissue sample available from the metastatic setting (preferably) for retrospective HER2 central analysis confirmed by central laboratory. An adequate sample of tumor tissue must be provided from either a newly acquired biopsy from a region that has not been previously irradiated or the most recent archival sample.
• Patients with Brain Metastases (BM): Eligible if either previously untreated or previously treated BM, provided there is no clinical indication for immediate local therapy. For untreated BM, lesions must be ≤2.0 cm in largest diameter; lesions \>2.0 cm require discussion with and approval from the Medical Monitor. Patients must not require \>3 mg/day of dexamethasone (or equivalent corticosteroid) for symptom control. If receiving anticonvulsants, the regimen must be stable for ≥14 days prior to first dose. A washout period prior enrollment of ≥3 weeks since stereotactic radiosurgery or gamma knife, whole-brain radiotherapy, or radiotherapy or surgery for spinal cord compression is required.
• Note: Patients with leptomeningeal disease may be eligible after discussion with the Medical Monitor.
• Adequate hematologic and end-organ function, defined by the following laboratory results (see protocol)
⁃ LVEF ≥ 50% within 28 days before Cycle 1 Day 1.
⁃ Life expectancy of ≥ 12 weeks at screening.
⁃ Adequate treatment washout period before first dose of study intervention, defined as (see protocol)
⁃ Male patients and female patients of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified highly effective method of contraception.
⁃ Access to a smartphone with internet connection that allows them to carry out the required assessments at the specified timepoints and with the following characteristics:
∙ Resilience PRO: Android 8.0 (or newer) OR iOS 15.0 (or newer)
‣ Cankado PRO-React: Android 13.0 (or newer) OR iOS 17.0 (or newer)
⁃ Only applicable in France: patients affiliated to the social security system.