Phase 3 patritumab deruxtecan study of HER3-directed ADC in HR+/HER2- breast cancer

This open-label, randomized Phase 3 trial, sponsored by Merck Sharp & Dohme LLC, evaluates whether patritumab deruxtecan—a HER3-directed antibody–drug conjugate delivering a topoisomerase I inhibitor—improves progression-free and overall survival versus physician’s choice in patients with unresectable locally advanced or metastatic HR-positive, HER2-negative breast cancer. Control regimens include paclitaxel (tubulin inhibitor), capecitabine (thymidylate synthase inhibitor), pegylated liposomal doxorubicin (DNA synthesis inhibitor), or trastuzumab deruxtecan (HER2-directed ADC with a topoisomerase I inhibitor; applicable where HER2-low), offered over 13 months. In today’s post-CDK4/6 setting, options often include endocrine therapy plus targeted agents (e.g., capivasertib for AKT-pathway–altered disease, alpelisib for PIK3CA-mutant) before moving to single-agent chemotherapy; T-DXd (for HER2-low) and sacituzumab govitecan are common later-line ADCs. This study tests whether a HER3-directed ADC can outperform those physician’s-choice options in an endocrine-resistant population.