128 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/Human Epidermal Growth Factor Receptor 2–Negative Breast Cancer

Background

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 plus chemotherapy followed by adjuvant pembrolizumab after surgery. The same approach may be used for hormone receptor-low–positive (HR-low+)/HER2-negative (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 progression-free survival (PFS) and overall survival (OS) benefits vs chemotherapy in patients with metastatic TNBC. TroFuse-032 (NCT06966700; EU CT 2024-520190-12) evaluates efficacy and safety of neoadjuvant pembrolizumab plus sac-TMT or chemotherapy followed by pembrolizumab plus chemotherapy in participants with early-stage TNBC or HR-low+/HER2– breast cancer.

Design and Methods

This phase 3, randomized, open-label study is enrolling participants aged 18 years and older with centrally confirmed untreated, high-risk, early-stage TNBC or HR-low+/HER2− breast cancer per ASCO/CAP guidelines. Participants are randomly assigned 1:1 to neoadjuvant pembrolizumab plus sac-TMT followed by pembrolizumab plus paclitaxel plus carboplatin (arm 1) vs pembrolizumab plus paclitaxel plus carboplatin followed by pembrolizumab plus doxorubicin or epirubicin plus cyclophosphamide (arm 2; Table). Surgery is performed 3 to 6 weeks after last dose of neoadjuvant treatment. Adjuvant therapy (Table) is initiated 60 or less days after surgery. Primary efficacy end points are pCR (ypT0/Tis ypN0) at surgery and event-free survival (EFS). Secondary end points include OS, pCR-no DCIS (ypT0 ypN0), distant progression– or distant recurrence–free survival, patient-reported outcomes, and safety.

Status

Enrollment is ongoing.