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.
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.
Patients with HER2-negative disease.
Subjects who, in the opinion of the investigator, are unable to comply with the protocol requirements or who have any comorbidity or condition that may hinder study follow-up, response evaluation, or the informed consent process, including inability to read and understand the local language of the study site sufficiently to interact effectively with study materials and tools (including digital applications).
History of other primary malignancy unless treated with curative intent with no evidence of active disease within 3 years before the first dose of study treatment and of low potential risk for recurrence. Exceptions include: basal cell carcinoma of the skin and squamous cell carcinoma of the skin that has undergone potentially curative therapy, adequately resected non-melanoma skin cancer, in situ cancer of the cervix, curatively treated ductal carcinoma in situ (DCIS), contralateral breast cancer, Stage 1, grade 1 endometrial carcinoma or other solid malignant tumors with an expected curative outcome after Medical Monitor approval.
Persistent toxicities that the investigator deems related to previous anti-cancer therapy (excluding alopecia), not yet resolved to grade ≤ 1 or baseline. Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study treatment may be included (e.g., hearing loss). Participants with stable Grade 2 toxicities (defined as no worsening to >Grade 2 for at least 3 months prior to enrollment and managed with standard of care treatment) may be eligible per the discretion of the investigator (e.g., Grade 2 chemotherapy-induced neuropathy).
Single group
Digital Health Tools
DevicePatients will be followed via digital health tools for proactive toxicity management, which consist of one mobile app and two devices: (1) CANKADO/Resilience app (depending on the country and site) accessed through the patient's phone; (2) A pulse oximeter that together with the digital health mobile app will allow self-tracking of vital parameters such as oxygen saturation and heart rate, potentially facilitating early ILD detection; and (3) A smartwatch to collect patient granular data. All three digital health tools/items are CE-marked medical devices, where relevant, used exclusively within their approved intended purpose, and not subject to any investigation of safety or performance within this study.
T-DXd
DrugT-DXd at 5.4 mg/kg will be administered as IV infusion q3w.
Pertuzumab
DrugPertuzumab will be administered at a loading dose of 840 mg on Day 1 of Cycle 1, followed by 420 mg in subsequent cycles, administered as IV q3w.
Efficacy of T-DXd as a first-line therapy - TFST
Time to first subsequent anti-cancer therapy (TFST) is defined as the time from the date of first dose of the study treatment to the date of i) first subsequent anti-cancer therapy after disease progression or discontinuation of maintenance treatment (in patients who discontinued due to treatment-related toxicities), or ii) death from any cause, whichever occurs first
Health-related quality of life
Time to 10% physical functioning deterioration, based on the EORTC QLQ-C30 Physical Functioning scale. Values range from 0 to 100. Higher scores mean a better outcome.
Adverse events (safety)
Occurrence /severity of AEs, laboratory abnormalities, discontinuation rates, dose reductions/interruptions
Percentage of any acute or delayed nausea and vomiting
Percentage of any acute or delayed nausea and vomiting or breakthrough anti-emetic use, in patients receiving prophylactic anti-emetic agents (combination regimen of 3 medicinal products)
Unplanned healthcare utilization
Composite of ER visits, unplanned hospitalizations and non-programed visits
Efficacy of T-DXd as a first-line therapy - PFS
Progression-free survival, defined as the time from the date of first dose to the date of first clinical or radiological progression or death due to any cause, whichever occurs first, as assessed by the investigators' assessments and according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria
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SOLTI Breast Cancer Research Group
Lead sponsor
Westdeutsche Studiengruppe GmbH (WSG)
Collaborator
UNICANCER
Collaborator
