TIP126 TroFuse-011: A Phase 3, Randomized, Open-Label Study of Sacituzumab Tirumotecan With or Without Pembrolizumab vs Treatment of Physician’s Choice for Previously Untreated Locally Recurrent Unresectable or Metastatic Triple-Negative Breast Cancer With PD-L1 Combined Positive Score <10

Background

The standard first-line therapy for most previously untreated locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) with PD-L1 combined positive score (CPS) less than 10 is chemotherapy alone. New therapeutic options with superior efficacy are needed. Sacituzumab tirumotecan (sac-TMT; MK-2870/SKB264) is a novel antibody-drug conjugate (ADC) composed of an anti–trophoblast cell surface antigen 2 (TROP2) monoclonal antibody coupled to a cytotoxic belotecan-derived topoisomerase I inhibitor payload via a unique bifunctional linker. Sac-TMT monotherapy has shown promising efficacy with a manageable safety profile in metastatic TNBC. There is strong biologic rationale supporting combination of an ADC with pembrolizumab regardless of PD-L1 expression. The TroFuse-011 study (NCT06841354) evaluates sac-TMT with or without pembrolizumab vs treatment of physician’s choice (TPC) in participants with previously untreated locally recurrent unresectable or metastatic TNBC with PD-L1 CPS less than10.

Design and Methods

Eligible participants (≥18 years) with centrally confirmed locally recurrent unresectable or metastatic TNBC, measurable disease per RECIST v1.1, ECOG performance status 0 or 1, and a tumor tissue sample evaluable for central PD-L1 and TROP2 testing are randomized 2:1:2 to receive sac-TMT 4 mg/kg every 2 weeks (arm A), sac-TMT 4 mg/kg every 2 weeks + pembrolizumab 400 mg every 6 weeks (arm B), or TPC (arm C). TPC consists of one of: paclitaxel, nab-paclitaxel, or gemcitabine plus carboplatin (Table). Primary end points are progression-free survival (PFS) per RECIST v1.1 as assessed by blinded independent central review (arm A vs C and arm B vs C) and overall survival (OS; arm A vs C). Secondary end points are 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) and duration of response, patient-reported outcomes, and safety. Tumor imaging occurs at baseline, every 8 weeks after randomization until week 48, and every 12 weeks thereafter.

Status

Enrollment is ongoing.