Abstract PS5-12-22: Trofuse-012: a phase 3, randomized study of adjuvant sacituzumab tirumotecan plus pembrolizumab vs treatment of physician’s choice in participants with triple-negative breast cancer who received neoadjuvant therapy and did not achieve a pathological complete response at surgery

Abstract Trophoblast cell surface antigen 2 (TROP2) expression is higher in triple-negative breast cancer (TNBC) vs other breast cancer subtypes, and high expression is associated with poor prognosis. Sacituzumab tirumotecan (sac-TMT; also known as MK-2870/SKB264) is a novel antibody-drug conjugate composed of anti-TROP2 antibody coupled to a cytotoxic belotecan derivative via a novel linker (average drug/antibody ratio, 7.4). In a prior phase 3 study (OptiTROP-Breast01), sac-TMT alone improved PFS (HR, 0.31; 95% CI, 0.22-0.45; P < 0.00001) and OS (HR, 0.53; 95% CI, 0.36-0.78; P = 0.0005) vs chemotherapy in participants with heavily pretreated advanced TNBC. The current standard of care (SOC) for patients with newly diagnosed, high-risk, early-stage TNBC is neoadjuvant pembrolizumab + chemotherapy followed by adjuvant pembrolizumab after surgery. Patients who do not achieve a pathological complete response (pCR) with the current SOC have higher rates of recurrence and mortality vs patients who achieve pCR. This study (NCT06393374) evaluates adjuvant sac-TMT plus pembrolizumab vs treatment of physician’s choice (TPC; pembrolizumab ± capecitabine) in participants with TNBC who received neoadjuvant therapy and did not achieve pCR at surgery. This phase 3, multicenter, open-label study is enrolling participants ≥18 years old with centrally confirmed TNBC per most recent American Society of Clinical Oncology/College of American Pathologists guidelines. Participants have non-pCR after ≥5 cycles of neoadjuvant pembrolizumab plus chemotherapy, including ≥1 cycle of anthracycline-based neoadjuvant therapy. Participants must provide tissue from the surgical specimen for central TROP2 assessment and be able to continue on adjuvant pembrolizumab. Randomization must be conducted ≤16 weeks from surgical resection (window may be extended in consult with sponsor). Participants are randomized 1:1 to pembrolizumab 400 mg Q6W for 5 doses + sac-TMT 4 mg/kg Q2W for 12 doses or TPC with pembrolizumab 400 mg Q6W for 5 doses ± capecitabine 1000-1250 mg/m2 BID on days 1-14 and days 22-35 every 42 days for 4 cycles until completion of therapy or disease recurrence, unacceptable toxicity, or withdrawal. Primary endpoint is invasive disease-free survival. Secondary endpoints are OS, distant recurrence-free survival, patient-reported outcomes, and safety. Enrollment began Q2 2024. Citation Format: H. L. McArthur, R. Dent, R. Hui, Y. Park, P. Schmid, J. Wei, J. A. Mejia, W. Pan, J. Cortés. Trofuse-012: a phase 3, randomized study of adjuvant sacituzumab tirumotecan plus pembrolizumab vs treatment of physician’s choice in participants with triple-negative breast cancer who received neoadjuvant therapy and did not achieve a pathological complete response at surgery [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 PS5-12-22.