Periodic Reporting for period 1 - GUIDE.MRD (GUIding multi-moDal thErapies against MRD by liquid biopsies - GUIDE.MRD)
Période du rapport: 2023-05-01 au 2024-04-30
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.
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.
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 assays cover a variety of analysed properties of the cfDNA, such as mutations, epigenetic features or copy number variations, with some being tumor-informed and some being tumor-agnostic. The available reference standards have been assessed in regard to the selected assays and it has been determined that there is a need for a novel universal reference standard. The novel reference standard is still under development and pending full characterization.
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.
A patient advisory board has been established covering all cancers and recruting countries in GUIDE.MRD to understand the needs of the patients living with or having lived through a cancer diagnosis and therapy. Key stakeholders have been identified and contact will be initiated to establish dialogue between relevant parties.
The current ctDNA assay landscape has been screened and all available assays have been identified and their properties summarized. The assays cover a variety of analysed properties of the cfDNA, such as mutations, epigenetic features or copy number variations, with some being tumor-informed and some being tumor-agnostic. The available reference standards have been assessed in regard to the selected assays and it has been determined that there is a need for a novel universal reference standard. The novel reference standard is still under development and pending full characterization.
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.
A patient advisory board has been established covering all cancers and recruting countries in GUIDE.MRD to understand the needs of the patients living with or having lived through a cancer diagnosis and therapy. Key stakeholders have been identified and contact will be initiated to establish dialogue between relevant parties.
The reference material under development is going to be fully characterized 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 initiated 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. 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.