T-DXd vs. T-DM1 in high risk HER2-positive patients with residual invasive breast cancer following neoadjuvant therapy (DESTINY-Breast05)

This is a global, multicenter, randomized, open-label, active-controlled, Phase 3 study of T-DXd versus T-DM1 in subjects with HER2-positive primary breast cancer (BC) who have residual invasive disease in breast or axillary lymph nodes with higher risk of recurrence, which includes subjects who were inoperable at disease presentation or had pathological node-positive status after neoadjuvant therapy. The primary objective is to compare invasive disease-free survival (IDFS) between T-DXd and T-DM1 treatment arms in this population. This study is designed to randomize at least 1600 subjects in a 1:1 ratio to receive T-DXd or T-DM1. Randomization will be stratified by the following factors: • Operative status at disease presentation, prior to neoadjuvant therapy (operable [clinical stages T1-3, N0-1, M0] vs inoperable [clinical stages T4, N0-3, M0 or T1-3, N2-3, M0]) • Tumor hormone receptor (HR) status (positive vs negative) • Post-neoadjuvant therapy pathologic nodal status (positive [ypN1-3] vs negative [ypN0]) • HER2-targeted neoadjuvant therapy approach (single vs dual)