45 A Phase 3 Randomized Study of Adjuvant Sacituzumab Tirumotecan Plus Pembrolizumab vs Treatment of Physician’s Choice in Patients With Triple-Negative Breast Cancer Who Received Neoadjuvant Therapy and Did Not Achieve a Pathological Complete Response at Surgery

45 A Phase 3 Randomized Study of Adjuvant Sacituzumab Tirumotecan Plus Pembrolizumab vs Treatment of Physician’s Choice in Patients 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 (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 (NCT05347134), sacituzumab tirumotecan alone improved progression-free survival (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 patients 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 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 sacituzumab tirumotecan plus pembrolizumab vs treatment of physician’s choice (pembrolizumab ± capecitabine) in patients with TNBC who received neoadjuvant therapy and did not achieve pCR at surgery.

Materials and Methods

This phase 3, multicenter, open-label study is enrolling patients 18 years and older with centrally confirmed TNBC per the most recent American Society of Clinical Oncology/College of American Pathologists guidelines. Patients have non-pCR after 5 or more cycles of neoadjuvant pembrolizumab plus chemotherapy, including 1 or more cycles of anthracycline-based neoadjuvant therapy. Patients must provide tissue from the surgical specimen for central TROP2 assessment and be able to continue on adjuvant pembrolizumab. Randomization must be conducted 12 weeks or less from surgical resection (window may be extended in consult with the sponsor). Patients are randomized 1:1 to pembrolizumab 400 mg every 6 weeks for 5 doses plus sacituzumab tirumotecan 4 mg/kg every 2 weeks for 12 doses or physician’s choice chemotherapy with pembrolizumab at 400 mg every 6 weeks for 5 doses with or without capecitabine at 1000 to 1250 mg/m2 twice daily on days 1 to 14 and days 22 to 35 every 42 days for 4 cycles until completion of therapy or disease recurrence, unacceptable toxicity, or withdrawal. Randomization is stratified by residual tumor and lymph node status, TROP2 expression, and intention to use capecitabine. 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 in Q2 2024.