DEFINITIVE Trial Reaches Major Milestone: All Centres Approved and More Than 50% Recruitment Achieved

The DEFINITIVE project, a landmark European Union-funded international phase III clinical trial evaluating the use of the HER2DX diagnostic assay to guide personalised treatment in early-stage HER2-positive breast cancer (BC), announces two major operational milestones at the ESMO Breast Cancer 2026 congress.

Approvals have been obtained in the 7 participating countries, 33 clinicals sites are now open for patient recruitment. The trial has reached over 50% of its recruitment target, marking a pivotal moment on the path toward to transforming HER2-positive BC treatment.

About the DEFINITIVE Project

The DEFINITIVE project is a 5-year, prospective, open-label, randomised, two-arm phase III international clinical trial conducted across 44 centres in 7 European member states and associated countries. The trial aims to demonstrate that personalising treatment decisions for patients with early-stage (stage II to IIIA) HER2-positive BC using the HER2DX genomic diagnostic assay can improve patients’ quality of life without compromising clinical outcomes.

The trial enrols 304 patients with stage II to IIIA HER2-positive BC, who are randomly assigned to two groups: one in which treatment is guided by the HER2DX assay, and one in which treatment follows standard physician-led local guidelines. This design allows a rigorous direct comparison of tumoral response, quality of life, safety, and cost-effectiveness analysis.

The DEFINITIVE consortium is part of the Cluster Pragmatic Clinical Trials on Minimally Invasive Diagnostics, funded by the European Union (Project Number 101136953). It is led by Principal Investigators Dr. Olga Martínez and Dr. Tomás Pascual from Hospital Clínic Barcelona (Spain).

Key Milestones: 33 Centres Open, 50% Recruitment Reached

In a significant operational achievement, 32 from 44 participating centres across Spain, Austria, France, Ireland, and Italy are now fully open and actively recruiting patients, while recruitment in Israel, an associated country, has already been completed.

The trial has exceeded 50% of its 304-patient recruitment target, demonstrating study momentum and feasibility, and remains on track to complete recruitment on schedule.

Recruitment is coordinated in Spain by SOLTI in France by Unicancer, in Germany by the West German Study Group (WSG), in Austria by the Austrian Breast & Colorectal Cancer Study Group (ABCSG), in Italy by the Università degli Studi di Padova-IEO, in Ireland by Cancer Research at University College Cork, and in Israel by SHEBA.

The HER2DX Diagnostic Assay

Developed by REVEAL GENOMICS, HER2DX is the world’s first diagnostic test formulated specifically for HER2+ BC. It is a standardised 27-gene expression test for patients with early-stage HER2+ BC.

HER2DX is a prognostic and predictive assay based on clinical and genomic data. The test integrates clinical information (i.e. tumor size and nodal status) with biological information tracking immune response, luminal differentiation, tumour cell proliferation, and expression of the HER2 17q12-21 chromosomal amplicon, including the ERBB2 gene.

HER2DX predicts:

• Risk of relapse score (high vs. low): the risk of recurrence in patients with newly diagnosed HER2+ BC.
• pCR likelihood score (high vs. medium vs. low): the likelihood of a patient responding to anti-HER2-based treatment with chemotherapy before surgery.
• ERBB2 score (high vs. medium vs. low): the quantitative expression of ERBB2 mRNA across HER2-negative, HER2-low and HER2-positive BC.

DEFINITIVE at ESMO Breast Cancer 2026

The DEFINITIVE project will feature prominently at the upcoming ESMO Breast Cancer 2026 congress. Giorgia Rapesta (Erasmus School of Health Policy & Management, Erasmus University Rotterdam, Rotterdam, Netherlands) presents the poster "Health policy and real-world strategies in early-stage HER2-positive BC: results from an international survey within the DEFINITIVE project" during the meeting.

This poster presents findings from an international survey conducted among 116 oncologists from 38 countries, providing key insights into the current landscape of health policy and real-world clinical strategies for managing early-stage HER2-positive BC across Europe.

A Step Forward for Precision Oncology

"Having all 33 centres recruiting across 7 countries and reaching more than 50% enrolment is a remarkable achievement. It reflects the commitment of our teams and patients, and the oncology community's belief in HER2DX as a tool to truly personalise BC treatment. ESMO 2026 is the perfect moment to share this momentum", says Dr. Tomás Pascual, Principal Investigator, Clínic Barcelona Comprehensive Cancer Centre.

The DEFINITIVE trial marks a crucial step in integrating genomic precision medicine into mainstream oncological practice across Europe, with the potential to redefine how HER2-positive BC is treated and managed in both clinical and health economic terms.

Further information: www.thedefinitivetrial.eu

Funded by the European Union. Views and opinions expressed are those of the author(s) only and do not necessarily reflect those of the European Union or HADEA. Neither the European Union nor the granting authority can be held responsible for them.

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