Standardization and clinical implementation of liquid biopsy assays - IMI's CANCER-ID
Authors: Klaus Pantel, Leon W. M. M. Terstappen, nicolo manaresi, Harry J. M. Groen, Menno Tamminga, Eduardus Schuuring, Ellen Heitzer, Michael R. Speicher, Bjorn Naume, jon amund kyte, thomas Schlange
Journal: Cancer Research (2019)

The innovative medicine initiative (IMI) project CANCER-ID (www.cancer-id.eu) is a 5 year (2014-2019) international public-private partnership of currently 40 partners from 14 countries, with the aim to evaluate technologies for Circulating Tumor Cell (CTC), circulating free tumor DNA (ctDNA), microRNA (miRNA) and exosome enrichment, isolation and analysis. At the core of CANCER-ID's activities are establishment of harmonized best practice protocols from patient sample collection, pre-analytical sample handling, sample and bioinformatics analyses down to the actionable information guiding patient selection and personalized treatment. CANCER-ID is furthermore testign and supporting development of standards for liquid biopsy as well as clinical implementation of liquid biopsy based protocols in the clinical setting. This included interaction with regulatory bodies in Europe (EMA InnovationTask Force) and the US (FDA Public-Private Partnership liaison) to support future approval of liquid biopsies in multi-centered worldwide clinical studies. During the clincial validation phase of the project, clinical-ready liquid biopsies protocols have been implemented in an observational study on the potential predictive value of monitoring treatment response to Immune Checkpoint Inhibition (ICI) in 180 NSCLC patients in the UMC Groningen, The Netherlands, as well as in two ICI-chemotherapy combination studies in triple-Negative BReast Cancer and Luminal B-type breast cancer, respectively, run by the University of Oslo, Norway (Alice NCT03164993 and ICON NCT03409198). Within both studies, blood has been collected at baseline and at follow-up visits for ctDNA and CTC analysis, including technical evaluation of CTC PD-L1 protein expression. The aim is to assess whether the allelic frequency of mutations identified by plasma NGS as a potential measure for Tumor Mutational Burden or the number of PD-L1 positive/overall CTC at different time points is indicative of treatment success. The studies aim at providing data to assess whehter clinical predictive information could be inferred from baseline number of detected mutations and PD-L1 expressing CTCs. Preliminary data of these analyses will be presented. As a follow-up activity of the IMI CANCER-ID program, the European Liquid Biopsy society (ELBS) is currently being established by Prof. Pantel at UKE Hamburg, Germany. The ELBS will be open to all interested liquid biopsy stakeholders worldwide as a platform for scientific exchange, further efforts to standardize technologies and protocols in the field as well as for the initiation of the new basic and clinical research projects with the aim to make liquid biopsies and integral part of clinical studies and patient care. This work is supported by IMI JU & EFPIA (grant no. 115749, CANCER-ID). Samples from patients and healthy volunteers, respectively, were collected under signed informed consent.