237TiP - GUIDE.MRD: A Consortium guiding multi-modal therapies against minimal residual disease (MRD) by liquid biopsy to assess implementation of circulating tumor DNA (ctDNA) in clinical practice to improve patient outcomes

Background

An integrated precision oncology approach that can guide the selection of personalized therapy is paramount to achieving improved outcomes in patients while maintaining responsible healthcare economics. Actionable precision oncology requires in vitro diagnostic tests that are sufficiently sensitive, accurate, reproducible, and reliable in the real-world setting with minimal risk of patient overtreatment or undertreatment. Liquid biopsies and specifically ctDNA based diagnostics provide a unique opportunity to optimize clinical decisions and thereby improve individual patient care. Such techniques could be particularly valuable in the adjuvant setting where multi-modal therapy (MMT) has curative potential. Multiple studies provide evidence that serial ctDNA monitoring can predict or detect recurrence earlier than conventional surveillance. However, as highlighted in the most recent ESMO ctDNA recommendations, the detection limit of current diagnostics to accurately report ctDNA fragments in peripheral blood remains a challenge. Importantly, it is currently unclear how to incorporate ctDNA as MRD biomarker or as a decision tool for treatment selection to improve cancer outcomes. GUIDE.MRD, a patient-centered precision oncology public-private partnership under the Innovative Health Initiative umbrella, is designed to improve the utility and clinical implementation of ctDNA as MRD biomarker and to evaluate the potential of novel decision tools to match patients to MMTs.

Trial design

Partners from academic, medical technology, pharmaceutical and patient advocacy sectors will join to (a) benchmark available ctDNA assays for sensitivity, specificity, and predictive value using reference material that closely mimic patient samples in the adjuvant setting, (b) to clinically validate the top performing ctDNA assay characteristics in patients with NSCLC, CRC and PDAC and develop patient-centric clinical implementation roadmaps, and (c) determine the utility of ctDNA assays as a prospective decision tool of clinical response and choice of MMT including novel combinations.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Universitaetsklinikum Hamburg-Eppendorf.

Funding

Innovative Health Initiative.

Disclosure

K. Pantel: Financial Interests, Personal, Invited Speaker, Research Presentation and Discussion: Abcam, Agena, Ipsen Pharma, Medac; Financial Interests, Personal, Advisory Board: Hello Healthcare, Sanofi; Financial Interests, Personal, Advisory Board, Research Presentation and Discussion: Menarini; Financial Interests, Personal, Advisory Board, Expert Input Forum: MSD; Financial Interests, Institutional, Other: Angle plc; Financial Interests, Institutional, Other, Clinical study: Boehringer Ingelheim; Financial Interests, Institutional, Other, UKE - European Liquid Biopsy Society (ELBS): ELBS; Financial Interests, Institutional, Other, EFPIA Partners of EU/IMI Cancer-ID consortium: UKE - European Liquid Biopsy Society (ELBS). C. Lindbjerg Andersen: Non-Financial Interests, Institutional, Funding: Natera, C2i Genomics. E. Schuuring: Financial Interests, Institutional, Research Grant: Abbott, Biocartis, AstraZeneca, Invitae/Archer, Bayer, Bio-Rad, Roche, Agena Bioscience, CC Diagnostics, MSD/MERCK, Boehringer Ingelheim; Financial Interests, Institutional, Advisory Board: MSD/Merck, AstraZeneca, Roche, Novartis, Bayer, BMS, Lilly, Amgen, Illumina, Agena Bioscience, CC Diagnostics, Janssen Cilag (Johnson&Johnson), Astellas Pharma; Financial Interests, Institutional, Invited Speaker: Bio-Rad, Seracare, Roche, Biocartis, Lilly, Agena Bioscience, Illumina; Financial Interests, Institutional, Other, Only travel expenses: BioRad, Biocartis, Ageno Sciences; Non-Financial Interests, Personal, Member of Board of Directors: Dutch Society of Pathology, European Society of Pathology, European Liquid Biopsy Society; Financial Interests, Personal and Institutional, Advisory Role: Advisory committee for assessment of molecular diagnostics (cieBOD; secretary/member), National guideline advisory committee member. N. Malats: Non-Financial Interests, Personal, Other, Partner GUIDE-MRD: Spanish National Cancer Research Centre (CNIO). E. Heitzer: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Institutional, Research Grant: Roche, Illumina, PreAnalytiX. E. Kiernan: Financial Interests, Personal, Full or part-time Employment: Illumina Inc. E. Chin: Financial Interests, Institutional, Full or part-time Employment: Revvity; Financial Interests, Institutional, Stocks/Shares: Revvity. J.C. Barrett: Financial Interests, Institutional, Full or part-time Employment: AstraZenenca. J.R. Kapp: Financial Interests, Personal, Full or part-time Employment: Amgen Inc.; Financial Interests, Personal, Stocks/Shares: Amgen Inc. M. Thomas: Financial Interests, Institutional, Full or part-time Employment: F. Hoffmann La Roche; Financial Interests, Institutional, Member: F. Hoffmann La Roche; Financial Interests, Institutional, Stocks/Shares: F. Hoffmann La Roche. M. Gerling: Financial Interests, Institutional, Local PI: IHI-EU project GUIDE.MRD. M. Reck: Financial Interests, Personal and Institutional, Invited Speaker: Amgen, AstraZeneca, BMS, Boehringer Ingelheim, GSK, Lilly, Mirati, MSD, Merck, Novartis, Regeneron, Sanofi, Roche; Financial Interests, Personal and Institutional, Speaker’s Bureau: Amgen, AstraZeneca, BMS, Boehringer Ingelheim, GSK, Lilly, Mirati, MSD, Merck, Novartis, Regeneron, Sanofi, Roche; Financial Interests, Personal and Institutional, Advisory Board: Amgen, AstraZeneca, BMS, Biontech, Boehringer Ingelheim, Daiichi Sankyo, Gilead, GSK, MSD, Mirati, Pfizer, Regeneron, Sanofi, Roche; Financial Interests, Personal and Institutional, Other, DMSB: Daiichi Sankyo, Sanofi. P. Hofman: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Qiagen, AbbVie, Novartis, Janssen; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Qiagen, AbbVie, Novartis, Janssen. J.T.J.N. Hiltermann: Financial Interests, Personal and Institutional, Other: Roche, BMS, MSD, Pfizer, CieBOM, GSK, Novartis, Merck Serono, Amgen; Financial Interests, Personal and Institutional, Advisory Role: AstraZeneca, Bristol Myers Squibb, Merck Sharp Dohme, Roche; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca, Hoffmann-La Roche. C. Alix-Panabières: Financial Interests, Personal, Other: Menarini, CTC technologies. M. Bolisetty: Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. M. Karasarides: Financial Interests, Institutional, Full or part-time Employment: Bristol Myers Squibb. All other authors have declared no conflicts of interest.