Evaluation of Trastuzumab Deruxtecan in Multi-Modality Treatment for HER2-Positive Oligometastatic Breast Cancer

The primary objective of this study is to determine the clinical efficacy of **trastuzumab deruxtecan** (T-DXd) as part of a multi-modality treatment in patients with HER2-positive oligo-metastatic breast cancer. This is clinically relevant as it aims to assess the potential of T-DXd to improve treatment outcomes in a specific subset of breast cancer patients characterized by limited metastatic spread, which may allow for more targeted therapeutic strategies.

Secondary objectives include:

• To determine the efficacy of T-DXd in achieving a clinical response along with the clearance of circulating tumor DNA (ctDNA) in patients with HER2-positive oligo-metastatic breast cancer.
• To evaluate the feasibility, safety, and tolerability of T-DXd as part of a multi-modality approach.

The clinical trial involves participants diagnosed with **HER2-positive breast cancer** with oligometastatic disease. The study population includes both male and female subjects, aged 18 years and older, who are in good general health as indicated by a World Health Organization performance status of 0 or 1. The trial does not involve a vulnerable population. Participants were selected based on specific criteria, including histologic proof of infiltrating HER2-positive breast cancer and measurable disease according to RECIST1.1. The trial population was not limited by lifestyle factors such as diet or physical activity. The sponsor has not provided information regarding the total number of participants in the study.

The clinical trial is designed to evaluate the **clinical efficacy** of **trastuzumab deruxtecan** (DS-8201a) as part of a multi-modality treatment in patients with **HER2-positive oligo-metastatic breast cancer**. This is a phase II, randomized, double-blind, controlled trial. The trial is expected to run until September 15, 2034, with recruitment having commenced on September 15, 2023. Participants will be involved in the study for a maximum treatment period of 12 months, receiving a maximum daily dose of 5.4 mg/kg of the investigational product via **intravenous infusion**.

The sequence of study visits begins with an inclusion (screening) visit, where eligibility is confirmed based on criteria such as histologic proof of infiltrating HER2-positive breast cancer, measurable disease according to RECIST1.1, and a WHO performance status of 0 or 1. Initial staging involves PET-CT and MRI scans. Follow-up visits will be scheduled to monitor treatment response and adverse events, with assessments including radiologic and metabolic responses, as well as the incidence and severity of adverse events according to CTCAE v5.0. The end-of-study visit will conclude the participant's involvement, assessing the primary endpoint of complete radiologic response as defined by RECIST1.1.

Participants may be withdrawn from the study early if they experience unacceptable toxicity, fail to comply with study procedures, or withdraw consent. The trial aims to provide comprehensive data on the efficacy and safety of DS-8201a in this patient population, contributing to the understanding of its role in the treatment of HER2-positive oligo-metastatic breast cancer.

The clinical trial involves the administration of **trastuzumab deruxtecan**, commercially known as DS-8201a, which is an investigational medication formulated as a **solution for infusion**. This pharmaceutical product is developed by Daiichi Sankyo, Inc. and is intended for use in patients with HER2-positive oligo-metastatic breast cancer. The active substance, trastuzumab deruxtecan, is a protein-based compound classified under the category "Protein - Other." The medication is administered via **intravenous infusion** at a dosage of 5.4 mg/kg. The treatment is scheduled to be administered every three weeks, with a maximum treatment period of 12 cycles.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on evaluating the clinical efficacy of DS-8201a as part of a multi-modality treatment approach. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol. The trial aims to assess the therapeutic potential of DS-8201a in the specified patient population, contributing to the understanding of its role in the treatment of HER2-positive oligo-metastatic breast cancer.

The clinical trial aims to assess the efficacy of **trastuzumab deruxtecan** (T-DXd) as part of a multi-modality treatment in patients with HER2-positive oligo-metastatic breast cancer. Efficacy will be primarily evaluated through the endpoint of complete radiologic response, as defined by RECIST 1.1 criteria. Secondary endpoints include complete radiologic response along with clearance of circulating tumor DNA (ctDNA), progression-free survival (PFS) as defined by RECIST 1.1, pathological complete response in patients undergoing resection of primary tumor and/or metastatic lesions after neo-adjuvant treatment, and complete metabolic response as defined by EORTC guidelines. Additionally, the trial will assess the preplanned loco-regional treatment performed without treatment-related delay within a window of 3 weeks, and the incidence and severity of adverse events, including interstitial lung disease (ILD), until 30 days after the last treatment administration. The incidence and severity of adverse events of grade ≥3 will also be evaluated using CTCAE v5.0 or Clavien-Dindo criteria in the case of surgical resection.