SYD985 vs. Physician's Choice in Participants With HER2-positive Locally Advanced or Metastatic Breast Cancer

A Multi-centre, Open-label, Randomized Clinical Trial Comparing the Efficacy and Safety of the Antibody-drug Conjugate SYD985 to Physician's Choice in Patients With HER2-positive Unresectable Locally Advanced or Metastatic Breast Cancer

The purpose of this study is to demonstrate that SYD985 [(vic-)trastuzumab duocarmazine] is superior to physician's choice in prolonging progression free survival.

This study is designed as a randomized, active-controlled, superiority study in patients with unresectable locally advanced or metastatic HER2-positive breast cancer. The patients should have had either progression during or after at least two HER2-targeting treatment regimens for locally advanced or metastatic disease or progression during or after (ado-)trastuzumab emtansine treatment.

Eligible patients will be randomly assigned (2:1) to receive SYD985 or physician's choice treatment until disease progression, unacceptable toxicity or study termination by the Sponsor. During treatment, patients will have to visit the clinical site to assess efficacy, quality of life (QoL), and safety using standardized criteria.

Main Inclusion Criteria:

• Female patients with histologically-confirmed, unresectable locally advanced or metastatic breast cancer;
• Patients should have had either progression during or after at least two HER2-targeting treatment regimens for locally advanced or metastatic disease or progression during or after (ado-)trastuzumab emtansine treatment for locally advanced or metastatic disease;
• HER2-positive tumor status;
• Patients must have measurable or non-measurable disease that is evaluable per RECIST 1.1;
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2;
• Estimated life expectancy > 12 weeks at randomization;
• Adequate organ function and blood cell counts.

Main Exclusion Criteria:

• Current or previous use of a prohibited medication as listed in the protocol;
• History of infusion-related reactions and/or hypersensitivity to trastuzumab, (ado-)trastuzumab emtansine;
• History of keratitis;
• Severe, uncontrolled systemic disease at screening;
• Left Ventricular Ejection Fraction (LVEF) < 50%, or a history of clinically significant decrease in LVEF during previous treatment with trastuzumab or (ado-)trastuzumab emtansine;
• Cardiac troponin value above the Upper Limit of Normal (ULN);
• History of clinically significant cardiovascular disease;
• Untreated brain metastases, symptomatic brain metastases, brain metastases requiring steroids to manage symptoms, or treatment for brain metastases within 8 weeks prior to randomization;
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.