PREDICT-RD: Postoperative Molecular Residual Disease by ctDNA Surveillance in TNBC with Residual Disease

Summary:

Triple-negative breast cancer (TNBC) accounts for approximately 15-20% of new breast cancer cases and has been associated with poor clinical outcomes. Recently, neoadjuvant chemo-immunotherapy has been established as the standard of care in patients with stage II/III TNBC and substantially improved response rates and survival outcomes. Despite treatment advances, the risk of recurrence remains high at approximately 35-50% within 3 years of treatment, especially for those with a higher residual cancer burden. Currently, there is no standard of care way to monitor for recurrence beyond clinical monitoring. Unfortunately, TNBC patients can have lingering cancer cells despite treatment. Thus, more studies are needed to improve disease relapse as well as advance surveillance strategies.

Detecting minimal residual disease (MRD) post-surgery is a promising approach to identifying patents at increased risk of recurrence after definitive therapy. These patients may benefit from an escalation of their treatment and remain potentially curable with effective systemic therapy. Circulating tumor DNA (ctDNA), a liquid biopsy, has emerged as a noninvasive approach for monitoring and detecting MRD. Technological advances have made this blood test even more sensitive and reliable. This phase II study, developed in conjunction with a nationally recognized breast cancer patient advocate, will collect ctDNA samples after definitive treatment for up to three years to evaluate the prevalence of MRD-positivity in TNBC patients with a high residual cancer burden. Those who have a positive ctDNA test, but negative imaging after completing planned standard of care treatment will have the option to be treated with Dato-DXd, an antibody-drug conjugate (ADC) which has shown promising efficacy in breast cancer. ADCs work by combining an antibody and chemotherapy agent to target and kill cancer cells like a heat seeking missile. Given the disproportionate impact of TNBC on Black women, the investigators have set their target accrual goal for Black women to at least 30% of all patients. This will be the first study to accurately estimate the MRD ‘therapeutic window’ for high-risk TNBC patients with residual disease after definitive therapy and to evaluate the role of Dato-DXd in the early TNBC setting for MRD-positive patients.

Trial Registration: ClinicalTrials.gov Identifier: NCT07069595