Evaluation of Patient Preference for Home Administration of Subcutaneous Fixed-Dose Combination of Pertuzumab and Trastuzumab in HER2-Positive Breast Cancer

The primary objective of this study is to evaluate **patient preference** for the fixed-dose combination of **pertuzumab** and **trastuzumab** (PH) for subcutaneous administration in the home setting during the cross-over period of the adjuvant phase. This is clinically relevant as it may enhance patient compliance and satisfaction, potentially improving treatment outcomes for individuals with early or locally advanced/inflammatory HER2-positive breast cancer.

Secondary objectives include:

• Evaluating the perception of healthcare professionals regarding time/resource use and convenience of PH FDC SC compared to P+H IV during the neoadjuvant phase.
• Collecting pathologic complete response (pCR) data post-surgery.
• Assessing Health-related Quality of Life (HRQoL) during the neoadjuvant phase and with PH FDC SC during the adjuvant phase.
• Evaluating the perception of healthcare professionals on time/resource use of PH FDC SC during the adjuvant cross-over period.
• Assessing HRQoL for participants treated with trastuzumab emtansine IV during the adjuvant phase.
• Evaluating the safety and tolerability of PH FDC SC and P+H IV during the neoadjuvant phase.
• Assessing the safety and tolerability of PH FDC SC administered in home and hospital settings during the cross-over and entire adjuvant treatment periods.
• Evaluating the safety and tolerability of trastuzumab emtansine IV during the adjuvant phase.
• Assessing patient choice of setting for the treatment continuation period.

The clinical trial involves a total of **315 participants** diagnosed with **early or locally advanced/inflammatory HER2-positive breast cancer**. The study population includes both female and male subjects, with an age range corresponding to categories 3 and 4, which typically represent adults and older adults. Participants were selected based on specific criteria, including an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and a confirmed diagnosis of HER2-positive breast cancer by a local laboratory. The trial includes individuals with a primary tumor greater than 2 cm in diameter or node-positive disease. Hormone receptor status of the primary tumor was determined following American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines. Adequate wound healing after breast cancer surgery was required to allow initiation of study treatment within nine weeks of the last systemic neoadjuvant therapy. The trial population also includes vulnerable groups, ensuring a comprehensive evaluation of the treatment's efficacy and safety across diverse demographics.

The clinical trial is designed as a **randomized**, open-label, multinational, multicenter study aimed at evaluating patient preference for home administration of a fixed-dose combination of **pertuzumab** and **trastuzumab** for subcutaneous administration in participants with early or locally advanced/inflammatory HER2-positive breast cancer. The trial will span an estimated duration from August 1, 2022, to September 25, 2025. Participants will be involved in the study for a maximum treatment period of up to 52 weeks, depending on the specific treatment regimen they are assigned to. The study will include several key phases, including a screening visit, multiple follow-up visits, and an end-of-study visit.

The sequence of study visits begins with the inclusion (screening) visit, where eligibility criteria are assessed, including an ECOG performance status of 0-1, confirmation of HER2-positive breast cancer, and adequate wound healing post-surgery. Following successful screening, participants will be randomized to receive either the investigational product or standard care. Follow-up visits will be conducted at regular intervals to monitor treatment efficacy, safety, and patient preference, as well as to collect data on health-related quality of life (HRQoL) and adverse events. The end-of-study visit will occur after the completion of the treatment period, where final assessments will be made, including the collection of data on patient preference for home versus hospital administration.

Participants may be withdrawn from the study prematurely if they experience significant adverse events, fail to comply with the study protocol, or withdraw consent. The primary endpoint of the study is the proportion of participants who prefer the administration of the fixed-dose combination in the home setting compared to the hospital setting, as assessed by the Patient Preference Questionnaire. Secondary endpoints include healthcare professional responses, HRQoL assessments, and the incidence of adverse events. The study aims to provide valuable insights into patient preferences and the feasibility of home administration of cancer therapies.

The clinical trial involves the administration of several experimental medications, each with specific pharmaceutical forms, dosages, and routes of administration. **Perjeta** (pertuzumab) is provided as a 420 mg concentrate for solution for infusion. It is administered via **intravenous infusion** with a maximum daily dose of 840 mg and a total dose of 5.88 g over a treatment period of up to 18 weeks. The product is specifically packaged and labeled for clinical trial use.

**Phesgo** is available in two formulations: a 1200 mg/600 mg solution for injection and a 600 mg/600 mg solution for injection. Both formulations contain the active substances **trastuzumab** and **pertuzumab**. The 1200 mg/600 mg formulation is administered subcutaneously with a maximum daily dose of 1200 mg and a total dose of 20.4 g over a 52-week period. The 600 mg/600 mg formulation is also administered subcutaneously, with a maximum daily dose of 600 mg and a total dose of 12 g over the same period.

**Kadcyla** (trastuzumab emtansine) is provided as a 160 mg powder for concentrate for solution for infusion. It is administered via intravenous infusion with a dosing regimen of 3.6 mg/kg, reaching a total dose of 50.4 mg/kg over a 42-week treatment period. The product is packaged and labeled appropriately for clinical trial use.

**Herceptin** (trastuzumab) is available as a 600 mg solution for injection in a vial. It is administered via intravenous infusion with a dosing regimen of 8 mg/kg, reaching a total dose of 56 mg/kg over an 18-week treatment period. The product is also packaged and labeled for clinical trial use.

Throughout the trial, participant compliance with the dosing schedules is monitored to ensure adherence to the treatment protocols. No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in the trial data provided.

Efficacy in this clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint focuses on the proportion of participants who prefer the administration of the fixed-dose combination of **pertuzumab** and **trastuzumab** for subcutaneous administration in the home setting compared to the hospital setting. This preference will be evaluated using Question 1 of the Patient Preference Questionnaire (PPQ).

Secondary endpoints include a variety of measures: responses from healthcare professionals to the Healthcare Professional Questionnaire (HCPQ) during the neoadjuvant phase, the proportion of participants achieving pathological complete response (pCR) as defined by the eradication of invasive disease in the breast and axilla, and health-related quality of life (HRQoL) assessed by the European Organization for Research and Treatment of Cancer core quality of life questionnaire (EORTC QLQ-C30) scores. Additionally, the incidence, nature, and severity of adverse events (AEs), serious adverse events (SAEs), and cardiac AEs will be monitored, with severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.

Data collection will occur at various stages of the trial, including the neoadjuvant and adjuvant phases, and will involve both patient-reported outcomes and clinical assessments. The trial is designed to provide comprehensive insights into patient preferences and the safety and efficacy of the treatment regimen in participants with early or locally advanced/inflammatory HER2-positive breast cancer.