TroFuse-032 study design: pembrolizumab plus sacituzumab tirumotecan or chemotherapy followed by pembrolizumab plus chemotherapy as neoadjuvant therapy for early-stage, triple-negative breast cancer or HR-low+/HER2− breast cancer

For most patients with high-risk, early-stage, triple-negative breast cancer (TNBC), neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab after surgery is considered the standard regimen, with the same approach increasingly being used for hormone receptor-low‒positive/human epidermal growth factor receptor 2–negative breast cancer (HR-low+/HER2− BC). However, lack of pathologic complete response (pCR) after neoadjuvant therapy is associated with higher risks of recurrence/mortality, representing an area of unmet need. Sacituzumab tirumotecan (sac-TMT; MK-2870/SKB264) is a trophoblast cell surface antigen 2 (TROP2)‒directed antibody-drug conjugate with a unique, bifunctional linker that maximizes payload delivery to tumor cells. TroFuse-032 (NCT06966700) is a phase III study evaluating neoadjuvant pembrolizumab plus sac-TMT followed by pembrolizumab plus chemotherapy versus neoadjuvant pembrolizumab plus chemotherapy for high-risk, early-stage, resectable TNBC or HR-low+/HER2− BC. Eligible participants will be randomized 1:1 to receive neoadjuvant pembrolizumab plus sac-TMT followed by pembrolizumab plus paclitaxel/carboplatin (arm 1) or neoadjuvant pembrolizumab plus paclitaxel/carboplatin followed by pembrolizumab plus doxorubicin or epirubicin plus cyclophosphamide (arm 2). After surgery, participants will receive adjuvant pembrolizumab (if pCR) or pembrolizumab-based treatment (if residual disease; Graphical Abstract). Primary endpoints are pCR (ypT0/Tis ypN0) and event-free survival. Secondary endpoints include overall survival, pCR (ypT0 ypN0), patient-reported outcomes, and safety. Enrollment is ongoing.Clinical trial registration NCT06966700 (ClinicalTrials.gov); EU CT 2024-520190-12 (EudraCT)