TIP127 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

Background

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 belotecan-derived topoisomerase I inhibitor payload via a unique bifunctional linker. In a prior phase 3 study (OptiTROP-Breast01), sac-TMT improved progression-free survival (PFS; HR, 0.31; 95% CI, 0.22-0.45; P <.00001) and overall survival (OS; HR, 0.53; 95% CI, 0.36-0.78; P = .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 plus 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. TroFuse-012 (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.

Design and Methods

This phase 3, multicenter, open-label study is enrolling participants 18 years or older with centrally confirmed TNBC per most recent ASCO/CAP guidelines. Participants have non-pCR after 5 or more cycles of neoadjuvant pembrolizumab plus chemotherapy, including 1 or more cycles of anthracycline-based neoadjuvant therapy. Participants must provide tissue for central TROP2 assessment. Randomization must be conducted less than 16 weeks from surgery (window may be extended in consult with sponsor). Participants are randomly assigned 1:1 to pembrolizumab 400 mg every 6 weeks for 5 doses plus sac-TMT 4 mg/kg every 2 weeks for 12 doses (arm 1) or TPC with pembrolizumab 400 mg every 6 weeks for 5 doses ± capecitabine 1000 to 1250 mg/m² twice a day on days 1 to 14 and days 22 to 35 every 42 days for 4 cycles (arm 2; Table). Primary end point is invasive disease-free survival. Secondary end points are OS, distant recurrence-free survival, patient-reported outcomes, and safety.

Status

Enrollment began Q2 2024.