PREDICT-RD: Postoperative molecular residual disease by ctDNA surveillance in TNBC with residual disease (TBCRC-071).

Abstract

TPS647 Background: Patients with residual triple-negative breast cancer (TNBC) post-neoadjuvant therapy, particularly those with higher residual cancer burden (RCB II/III), remain at high risk of recurrence despite standard adjuvant therapy. Current post-treatment surveillance relies primarily on clinical follow-up and imaging, which have limited sensitivity to detect disease at a subclinical stage and rarely enable early therapeutic intervention. Circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) assessment allows detection of tumor-derived DNA in the absence of radiographic disease and offers a framework to identify patients at high risk of recurrence, who may be candidates for early, biomarker-informed treatment escalation prior to overt metastatic recurrence. PREDICT-RD is designed to evaluate the clinical implications of post-surgical ctDNA surveillance in patients with high-risk, early-stage TNBC. We hypothesize that longitudinal monitoring with a tumor-informed, high sensitivity ctDNA assay will identify an MRD-only state in at least 10% of patients, defined by ctDNA positivity in the absence of clinical or radiographic recurrence. A secondary objective is to assess outcomes among patients with ctDNA-detected molecular relapse who undergo adjuvant treatment escalation with datopotamab deruxtecan (Dato-DXd). Dato-DXd is an antibody-drug conjugate composed of a monoclonal antibody targeting TROP2 linked to a topoisomerase I inhibitor payload. In TNBC, Dato-DXd has demonstrated a manageable safety profile and promising efficacy, including an improvement in median PFS of 5.3 months over SoC chemotherapy in the first line setting for patients who are not candidates to receive immunotherapy (TROPION-Breast02). Methods: PREDICT-RD (TBCRC-071) is a prospective phase II, interventional, open-label, single-arm, multi-center study. The trial will enroll 78 patients with Stage II or III TNBC with residual disease (RCB II/III) following neoadjuvant chemo-immunotherapy and surgery. Patients will undergo serial blood sampling for ctDNA assessments using a clinically available tumor-informed personalized assay (Signatera Genome, Natera, Inc.) at predefined intervals during adjuvant therapy and subsequent surveillance. ctDNA test results will be disclosed to both the treating provider and the patient. A positive ctDNA result will prompt consideration of imaging for distant disease. The primary endpoint is the prevalence of MRD-only relapse. Patients meeting these criteria will be considered for treatment escalation with Dato-DXd (up to eight cycles), with ctDNA clearance as a secondary endpoint. Patient-reported fear of recurrence and quality of life will be serially evaluated. Post-treatment surveillance will continue for up to three years following initial consent. Recruitment is anticipated to begin in early 2026 (NCT07069595). Clinical trial information: NCT07069595 .