GUIding multi-moDal thErapies against MRD by liquid biopsies - GUIDE.MRD

Projektinformationen

GUIDE.MRD

ID Finanzhilfevereinbarung: 101112066

DOI

10.3030/101112066

EK-Unterschriftsdatum 17 Mai 2023

Startdatum 1 Mai 2023

Enddatum 30 April 2028

Finanziert unter

• Health

Gesamtkosten

€ 34 948 425,41

EU-Beitrag

€ 17 660 955,00

Koordiniert durch

UNIVERSITAETSKLINIKUM HAMBURG-EPPENDORF
Germany

Periodic Reporting for period 2 - GUIDE.MRD (GUIding multi-moDal thErapies against MRD by liquid biopsies - GUIDE.MRD)

Berichtszeitraum: 2024-05-01 bis 2025-10-31

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

The detection of remaining tumor cells after surgery and/or therapy poses a challenge in the clinical context. This so-called minimal residual disease (MRD) can affect the course of the disease by advancing metastasis or relapse of the cancer. Therefore, it is important to detect the MRD as early, as confidently and as minimally invasively as possible. Liquid biopsy refers to the use of body fluids (for example the blood) and has opened a new diagnostic avenue in oncology. It is known that tumors and tumor cells shed minute amounts of DNA into the blood stream, called cell-free circulating tumor DNA (ctDNA). However, despite many circulating tumor DNA diagnostics being developed, there is a lack of standardization, harmonization, and robust data to demonstrate clinical validity.

GUIDE.MRD aims to make use of the assessment of ctDNA in the blood as an MRD marker to improve the outcome of patients with colorectal cancer, lung cancer and pancreatic cancer, and to advance the personalized care of each patient.

The GUIDE.MRD project will examine ctDNA liquid biopsies with four main objectives:
1. Identify, compare and rank the best diagnostic tests available for ctDNA-based MRD testing.
2. Evaluate top-ranking ctDNA tests using clinical samples from lung, colon, and pancreatic cancer patients to develop a roadmap for using these tests in routine cancer patient care.
3. Assess how ctDNA tests can guide healthcare professionals into choosing the right treatments or multi-modal treatment combinations for their patients.
4. Reach a consensus with healthcare professionals, patient groups and other key stakeholders to implement ctDNA testing into clinical routine.

GUIDE.MRD is a consortium of leading academics, technology companies, pharmaceutical companies, and experts in multi-stakeholder engagements. With robust engagement with regulatory authorities, payers and importantly patients themselves, the consortium will develop recommendations and guidelines based on objective data to use ctDNA diagnostics to guide multi-modal therapy selection to improve patient outcomes.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

Objective 1: Identify, compare and rank the best diagnostic tests available for ctDNA-based MRD testing.
The current ctDNA assay landscape has been screened and all available assays have been identified and their properties summarized. The novel reference standard has been developed and has already been used for technical benchmarking of major ctDNA test providers. First results are available and technical benchmarking will continue to identify the top-performing tests.

Objective 2: Evaluate top-ranking ctDNA tests using clinical samples from lung, colon, and pancreatic cancer patients to develop a roadmap for using these tests in routine cancer patient care.
The multi-center prospective clinical studies (GUIDE.MRD-01-through-03) that aim to collect longitudinal samples from patients with colorectal cancer, lung cancer and pancreatic cancer have been initiated and patient recruitment as well as sample collection are ongoing. Partners from 10 centres are recruiting. The sample indicative for MRD (i.e. after curative intended treatment) will then be used for the clinical evaluation of the top-ranking ctDNA tests that are selected from the analytical benchmarking. Standard operating procedures for sample handling, processing and quality control protocols have been developed in consensus with all participating partners as well as the patient advisory board and are established at all sites. A GUIDE.MRD data repository has been implemented and will be activated for the GUIDE.MRD-01-through-03 studies soon. After the clinical validation of the assays, the consortium will be able to provide a patient-centred roadmap for the clinical implementation of the assays.

Objective 3: Assess how ctDNA tests can guide healthcare professionals into choosing the right treatments or multi-modal treatment combinations for their patients.
The path to the GUIDE.MRD-05-RANDOM randomized clinical trial is paved by the benchmarking work that is currently undergoing. The results from the clinical studies will be used to guide the healthcare professionals into making educated treatment decisions for their patients, improving their outcomes.

Objective 4: Reach a consensus with healthcare professionals, patient groups and other key stakeholders to implement ctDNA testing into clinical routine.
The GUIDE.MRD patient advisory board of more than 10 patients and patient representatives exists and guides the consortium by proving the perspective and the needs of the patients living with or having lived through a cancer diagnosis and therapy. Key (international) stakeholders have been identified and first discussions are ongoing. The optimal healthcare pathway has been described and was accepted as an abstract online publication for ASCO 2025 (doi: 10.1200/JCO.2025.43.16_suppl.e23032)

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

The novel reference material has been confirmed to be suitable for ctDNA assay benchmarking and can be used for future implementation of ctDNA assays and diagnostics into clinical routines. The here provided framework also establishes the methodology for validation and standardization in the context of precision oncology. This will pave the way for the implementation in clinical decision making and personalized oncology. The GUIDE.MRD project will address the need for early relapse detection and therapy response, influencing further research and healthcare plans. Moreover, the clinical studies established and ongoing are large, multi-center studies with approximately 1,000 patients planned for enrollment. The project can serve as a role model for further projects. With the results from the benchmarking and clinical studies, a randomized clinical trial (GUIDE.MRD-05-RANDOM) will be initiated to fully determine the possibility of integration of ctDNA analyses into clinical decision making and how the results can guide healthcare professionals in the choice of multimodal therapy and thus resulting in improved patient care. Furthermore, additional risk assessment through ctDNA testing can lead to better (patient-centric) outcomes for those affected by cancer. The ideal healthcare has been co-created with different stakeholders. By assessing the treatment response, unnecessary treatment can be reduced, lessening the burden for the patient, but also for other stakeholders such as the payers.

GUIDE.MRD Consortium Partners