PREDICT-RD: ctDNA Surveillance in TNBC With Residual Disease

Not Applicable

Not yet recruiting

• Conditions: Breast Cancer; Residual Disease; Triple Negative Breast Cancer (TNBC); Stage II/III
• Interventions: Drug: Datopotamab deruxtecan; Diagnostic Test: Circulating tumor DNA (ctDNA) testing

• Registration Number: NCT07069595
• Lead Sponsor: UNC Lineberger Comprehensive Cancer Center

Brief Summary

This is a Phase II, interventional, prospective, single-arm, multi-center study that will enroll patients with stage II/III triple negative breast cancer (TNBC) who have residual cancer burden (RCB) II/III after conventional neoadjuvant chemo-immunotherapy followed by surgery. Technological advances in ctDNA assays have improved both the sensitivity and reliability of molecular residual disease (MRD) detection to enable real-time measurement with clinical-grade assays.

The primary objective of this study will be to evaluate ctDNA-based MRD status in high-risk, early-stage TNBC patients by defining the proportion of TNBC patients with MRD-only recurrence (ctDNA positive without radiographically measurable recurrence) during post-surgery surveillance. The secondary objectives will evaluate the safety, preliminary efficacy, and survival outcomes of using Dato-DXd in participants with MRD-only TNBC.

Dato-DXd is an investigational antibody-drug conjugate (monoclonal antibody specific for TROP2 and a topoisomerase I (Topo-1) inhibitor) that has demonstrated promising efficacy in TNBC patients with a manageable safety profile.

Detailed Description

Despite treatment advances, patients with II/III triple negative breast cancer (TNBC) residual disease post-neoadjuvant therapy, particularly patients with higher residual cancer burden (RCB II/III), remain at high risk for developing recurrence. Furthermore, early detection of relapse risk, when the residual disease burden is micrometastatic (defined here as undetectable by standard cross-sectional imaging), provides a chance for disease eradication whereas macrometastatic disease (i.e., detectable on standard cross-sectional imaging) is generally considered to be non-curable.

There are no standard of care (SOC) surveillance strategies for early detection of micrometastatic disease in high-risk TNBC beyond clinical monitoring. Detecting molecular residual disease (MRD) is a promising approach to identifying patients at increased risk of recurrence after definitive therapy, who may benefit from the escalation of their treatment and remain potentially curable with effective systemic therapy.

Study Timeline

• Status Verified: 2025-07
• Study First Submitted: 2025-07-07
• Study First Submitted QC: 2025-07-07
• Last Update Submitted: 2025-07-07
• Study First Posted: 2025-07-16
• Last Update Posted: 2025-07-16
• Study Start: 2025-09-01
• Primary Completion: 2028-11
• Study Completion: 2028-11-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 78

Inclusion Criteria

Written informed consent was obtained to participate in the study, and HIPAA authorization for the release of personal health information.

• Participant is willing and able to comply with study procedures based on the judgment of the investigator.
• Age ≥ 18 years at the time of consent.
• Histological confirmation of TNBC defined by ER/PR <10%, HER2 0-1+ by IHC or 2+ by IHC and fluorescence in situ hybridization (FISH) negative.
• Stage II/III TNBC treated with neoadjuvant systemic therapy AND have residual disease defined as RCB II/III at time of surgery.
• Baseline staging scans at the discretion of the treating physician and demonstrate no evidence of metastatic disease.
• The participant must have archival diagnostic tissue and/or surgical resection tissue Available.
• Participants are willing and able to comply with study procedures based on the judgment of the investigator.

Exclusion Criteria

• Participants are pregnant or breastfeeding.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Patients with higher residual cancer burden	Datopotamab deruxtecan	Participants with stage II/III triple negative breast cancer (TNBC) and residual disease post-neoadjuvant therapy, particularly patients with higher residual cancer burden (RCB II/III), remain at high risk for developing recurrence.
Patients with higher residual cancer burden	Circulating tumor DNA (ctDNA) testing	Participants with stage II/III triple negative breast cancer (TNBC) and residual disease post-neoadjuvant therapy, particularly patients with higher residual cancer burden (RCB II/III), remain at high risk for developing recurrence.

Primary Outcome Measures

Name	Time	Method
The proportion of triple negative breast cancer (TNBC) with molecular residual disease (MRD)	Up to 3 years after registration	The number of participants with triple negative breast cancer (TNBC) with molecular residual disease (MRD) only recurrence, which is defined as ctDNA positivity without radiographically measurable recurrence, during post-surgery surveillance.

Secondary Outcome Measures

Name	Time	Method
The time between Circulating tumor DNA (ctDNA) positivity and clinically proven relapse	Up to 3 years after registration	ctDNA levels will be measured every 6 weeks during adjuvant and/or Dato-DXd therapy and every 12 weeks thereafter.
Duration of Circulating tumor DNA (ctDNA) clearance	Up to 3 years after registration	Duration of ctDNA clearance will be defined as the time from the first confirmed clearance (for negative test after positive results) to the date of confirmed positivity.
Circulating tumor DNA (ctDNA) clearance with Dato-DXd	Up to 3 years after registration	ctDNA clearance in participants who receive Dato-DXd will be defined as the proportion of participants who convert from ctDNA positive to negative after initiation of Dato-DXd.
Toxicity of Dato-DXd	Up to 3 years after registration	Toxicity of Dato-DXd treatment will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. NCI-CTCAE is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.
Recurrence Free Survival (RFS) for ctDNA-positive and ctDNA-negative disease.	Up to 3 years after registration	RFS will be measured from the day of the first circulating tumor DNA (ctDNA) measurement to documented recurrence of disease in participants with ctDNA-positive and ctDNA-negative disease.
Recurrence Free Survival (RFS) - Dato-DXd	Up to 3 years after registration	RFS will be measured from the day of the first circulating tumor DNA (ctDNA) measurement to documented recurrence of disease in participants who receive Dato-DXd.
Overall Survival (OS) - ctDNA-positive and ctDNA and negative disease.	Up to 3 years after registration	OS will be measured from the day of the first ctDNA measurement to death from any cause in participants with ctDNA-positive and ctDNA-negative disease.
Overall Survival (OS) - for ctDNA-positive and ctDNA-negative disease.	Up to 3 years after registration	OS will be measured from the day of the first ctDNA measurement to death from any cause in participants who receive Dato-DXd.

Trial Locations

Locations (1)

UNC Lineberger Comprehensive Cancer Center; 🇺🇸 Chapel Hill, North Carolina, United States