Abstract PS5-08-18: 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

Abstract 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) 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 derivative, topoisomerase I inhibitor payload via a novel 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 ± pembrolizumab vs treatment of physician’s choice (TPC) in participants with previously untreated locally recurrent unresectable or metastatic TNBC with PD-L1 CPS 10. Trial design: Eligible participants (≥18 y) with centrally confirmed locally recurrent unresectable or metastatic TNBC, measurable disease per RECIST v1.1, ECOG PS 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 (Arm A), sac-TMT + pembrolizumab (Arm B), or TPC (Arm C; Table). Primary endpoints are PFS per RECIST 1.1 as assessed by BICR (Arm A vs C and Arm B vs C) and OS (Arm A vs C). Secondary endpoints are PFS (Arm B vs A), OS (Arm B vs C and Arm B vs A), ORR (Arm A vs C and Arm B vs C) and DOR, patient-reported outcomes, and safety. Tumor imaging occurs at baseline, Q8W after randomization until week 48, and Q12W thereafter. Enrollment is ongoing. Citation Format: A. Bardia, X. Peng, K. L. Smith, J. A. Mejia, H. S. Rugo. 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 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 PS5-08-18.