Merck has launched a pivotal Phase 3 clinical trial evaluating the combination of sacituzumab tirumotecan (MK-2870) and pembrolizumab as adjuvant therapy for patients with triple-negative breast cancer (TNBC) who have residual disease following neoadjuvant treatment. The randomized, open-label study will compare this investigational combination against treatment of physician's choice in a patient population with significant unmet medical needs.
Trial Design and Objectives
The Phase 3 trial is designed to enroll participants with triple-negative breast cancer who received neoadjuvant therapy but did not achieve a pathological complete response (pCR) at surgery. This patient population represents a high-risk group with residual disease that requires effective adjuvant treatment strategies.
The primary objective focuses on comparing sacituzumab tirumotecan plus pembrolizumab to treatment of physician's choice with respect to invasive disease-free survival (iDFS) per investigator assessment. The control arm consists of pembrolizumab monotherapy or pembrolizumab plus capecitabine, representing current standard-of-care options for this patient population.
Therapeutic Approach
The investigational combination leverages two distinct mechanisms of action. Sacituzumab tirumotecan functions as an antibody-drug conjugate, while pembrolizumab provides immune checkpoint inhibition through PD-1 blockade. This dual approach aims to address the aggressive nature of triple-negative breast cancer through targeted cytotoxic delivery combined with immune system activation.
The study hypothesis posits that sacituzumab tirumotecan plus pembrolizumab will demonstrate superior invasive disease-free survival compared to treatment of physician's choice per investigator assessment.
Clinical Significance
Triple-negative breast cancer represents one of the most challenging breast cancer subtypes, characterized by the absence of estrogen receptor, progesterone receptor, and HER2 expression. Patients who do not achieve pathological complete response following neoadjuvant therapy face particularly poor prognosis, highlighting the critical need for effective adjuvant treatment options.
The Phase 3 trial design reflects the scale typical of pivotal studies, with researchers planning to evaluate treatment efficacy in a large patient population, usually ranging from 1,000 to 5,000 participants. This substantial enrollment will provide the statistical power necessary to detect meaningful differences in invasive disease-free survival between treatment arms.
