PREDICT-RD: ctDNA Surveillance in TNBC With Residual Disease

Official title

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

Overview

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.

Interventions

• Drug Datopotamab deruxtecan
  Dato-DXd is administered adjuvantly at 6 mg/kg IV for eight cycles.
• Diagnostic test Circulating tumor DNA (ctDNA) testing
  Circulating tumor DNA (ctDNA) testing is a type of biopsy that analyzes fragments of DNA shed by cancer cells into the bloodstream. These fragments, known as ctDNA, can provide valuable information about the genetic makeup of a tumor without needing a traditional tissue biopsy.

Primary outcome measures

• The proportion of triple negative breast cancer (TNBC) with molecular residual disease (MRD) [Time frame: Up to 3 years after registration]

Secondary outcome measures (8)

• The time between Circulating tumor DNA (ctDNA) positivity and clinically proven relapse [Time frame: Up to 3 years after registration]
• Duration of Circulating tumor DNA (ctDNA) clearance [Time frame: Up to 3 years after registration]
• Circulating tumor DNA (ctDNA) clearance with Dato-DXd [Time frame: Up to 3 years after registration]
• Toxicity of Dato-DXd [Time frame: Up to 3 years after registration]
• Recurrence Free Survival (RFS) for ctDNA-positive and ctDNA-negative disease. [Time frame: Up to 3 years after registration]
• Recurrence Free Survival (RFS) - Dato-DXd [Time frame: Up to 3 years after registration]
• Overall Survival (OS) - ctDNA-positive and ctDNA and negative disease. [Time frame: Up to 3 years after registration]
• Overall Survival (OS) - for ctDNA-positive and ctDNA-negative disease. [Time frame: Up to 3 years after registration]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• UNC Lineberger Comprehensive Cancer Center — Chapel Hill

Identifiers

NCT: NCT07069595 · LCCC2215

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗