TroFuse-011 study design: sacituzumab tirumotecan with or without pembrolizumab for advanced triple-negative breast cancer with PD-L1 CPS <10.

Patients with advanced TNBC with PD-L1 CPS < 10 are typically treated with chemotherapy and experience poor outcomes. 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. Combining sac-TMT with immunotherapy may improve outcomes given their complementary respective direct cytotoxic and immune-mediated antitumor effects regardless of tumor PD-L1 expression. The TroFuse-011 study evaluates sac-TMT with/without pembrolizumab versus treatment of physician's choice (TPC; paclitaxel, nab-paclitaxel, or gemcitabine plus carboplatin) in previously untreated, centrally confirmed, locally recurrent unresectable or metastatic TNBC with PD-L1 CPS <10. Eligible adults with measurable disease per RECIST version 1.1, ECOG PS 0/1, and tumor tissue sample for central PD-L1 and TROP2 testing will be randomized to receive sac-TMT (arm A), sac-TMT plus pembrolizumab (arm B), or TPC (arm C). Primary endpoints include progression-free survival (PFS; arm A vs C and arm B vs C) and overall survival (OS; arm A vs C). Secondary endpoints include PFS (arm B vs A), OS (arm B vs C and arm B vs A), objective response rate (arm A vs C and arm B vs C), duration of response, patient-reported outcomes, and safety. Enrollment is ongoing.Clinical trial registration: www.clinicaltrials.gov identifier is NCT06841354.