Abstract PS5-12-25: Trofuse-032: a phase 3, randomized study of pembrolizumab plus sacituzumab tirumotecan or chemotherapy followed by pembrolizumab plus chemotherapy for early-stage triple-negative breast cancer or hormone receptor-low-positive (HR-low+)/ human epidermal growth factor receptor 2-negative (HER2−) breast cancer

Abstract Trophoblast cell surface antigen 2 (TROP2) is highly expressed in triple-negative breast cancer (TNBC) and is associated with poor prognosis. Current standard of care for high-risk, early-stage TNBC is neoadjuvant pembrolizumab (pembro) plus chemotherapy (chemo) followed by adjuvant pembro after surgery. The same approach may be used for HR-low+/HER2− breast cancer. Patients with TNBC or HR-low+/HER2− breast cancer without a pathological complete response (pCR) after neoadjuvant therapy have higher risks of recurrence and mortality. Sacituzumab tirumotecan or sac-TMT (also known as MK-2870/SKB264), a novel antibody-drug conjugate composed of an anti-TROP2 antibody coupled to a cytotoxic belotecan derivative via a novel linker, has demonstrated significant PFS and OS benefits vs chemo in patients with metastatic TNBC. TroFuse-032 (NCT06966700; EU CT 2024-520190-12) evaluates efficacy and safety of neoadjuvant pembro plus sac-TMT or chemo followed by pembro plus chemo in participants with early-stage TNBC or HR-low+/HER2− breast cancer. This phase 3, randomized, open-label study is enrolling participants aged ≥18 y with centrally confirmed untreated, high-risk, early-stage TNBC or HR-low+/HER2− breast cancer per ASCO/CAP guidelines. Participants are randomized 1:1 to neoadjuvant pembro plus sac-TMT followed by pembro plus paclitaxel plus carboplatin (arm 1) vs pembro plus paclitaxel plus carboplatin followed by pembro plus doxorubicin or epirubicin plus cyclophosphamide (arm 2; Table). Surgery is performed 3-6 wk after last dose of neoadjuvant treatment. Adjuvant therapy (Table) is initiated ≤60 d after surgery. Primary efficacy endpoints are pCR (ypT0/Tis ypN0) at surgery and event-free survival (EFS). Secondary endpoints include OS, pCR-no DCIS (ypT0 ypN0), distant progression- or distant recurrence-free survival, patient-reported outcomes, and safety. Enrollment is ongoing. Citation Format: N. Harbeck, J. Wei, F. Beca, J. A. Mejia, P. Schmid. Trofuse-032: a phase 3, randomized study of pembrolizumab plus sacituzumab tirumotecan or chemotherapy followed by pembrolizumab plus chemotherapy for early-stage triple-negative breast cancer or hormone receptor-low-positive (HR-low+)/ human epidermal growth factor receptor 2-negative (HER2−) breast cancer abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-12-25.