Abstract 159TiP
Background
In routine practice, the evaluation of treatment response in metastatic (m)CRC largely relies on serial imaging scans. Evidence has recently emerged suggesting that ctDNA may be a reliable biomarker to monitor mCRC evolution. Nevertheless, evidence on the potential of liquid biopsy in this setting is still low quality, mostly consisting of retrospective studies.
Trial design
COPERNIC is an international, multicenter clinical trial, consisting of a pilot study and a follow-on randomised trial. The pilot study (herein described) aims to confirm the predictive potential of early ctDNA dynamics, and inform the design of a larger ctDNA-driven trial. In this study, advanced CRC patients who are candidates for ≥3rd lines of systemic therapy undergo blood sample collection at pre-defined time points during treatment (D1, D15 and D29 for 2- or 4-weekly regimens; D1, D22 and D43 for 3-weekly regimens) and at each imaging assessment. ctDNA analyses are carried out in a central laboratory (Foundation Medicine Inc, FMI) with the FoundationOne Liquid CDx and FoundationOneMonitor assays, using ctDNA tumor fraction (TF), a composite method combining aneuploidy, somatic prediction, and alteration frequency. ctDNA TF changes during treatment are correlated with radiological response (as assessed every 8-12 weeks by RECIST v1.1). A blinded, independent central radiological review is planned. The primary objective is to select the optimal time point and cut-off value for early ctDNA changes (at D15/D22) to predict progressive disease as best radiological response with a high positive predictive value. The cut-off value for ctDNA TF will be defined based on non-parametric ROC-curves with bootstrapping. Based on a target sensitivity of 95%, a target specificity of 90%, a maximum error on both the false positive and the false negative fraction of 8%, a confidence level of 95%, and bearing in mind the expected radiologic response for chemorefractory CRC, 109 patients are needed to be screened to have 87 assessable patients. COPERNIC is sponsored by the Institut Jules Bordet, and supported by Roche and FMI. Recruitment is open at 13 sites across Belgium and France. The study is registered with ClinicalTrials.gov (NCT05487248).
Clinical trial identification
NCT05487248; First posted on August 4, 2022.
Legal entity responsible for the study
Institut Jules Bordet.
Funding
Roche and Foundation Medicine Inc.
Disclosure
T. Aparicio: Financial Interests, Personal, Invited Speaker, 2022: Servier; Financial Interests, Personal, Invited Speaker, 3 Conferences: Pierre Fabre; Financial Interests, Personal, Advisory Board, 2 Board in 2022 and 2023: BMS; Financial Interests, Personal, Invited Speaker, 1 conference: MSD; Non-Financial Interests, Leadership Role, 2021-2024: Fédération Francophone de Cancérologie Digestive. P. Artru: Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Roche, Servier, Pierre Fabre, BMS; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Expert Testimony: Merck Serono. M. Ben Abdelghani: Financial Interests, Personal, Invited Speaker: Incyte, Servier, Pierre Fabre; Financial Interests, Personal, Advisory Board: Merck, BMS, Bayer; Financial Interests, Institutional, Advisory Board: Deciphera. B. Chibaudel: Financial Interests, Personal, Expert Testimony: Amgen, BeiGene, Biocartis, Lilly, Merck, MSD, Pfizer, Pierre Fabre, Roche, SeqOne, Sanofi, Servier, Takeda; Financial Interests, Personal, Advisory Board: Bayer. K. Geboes: Financial Interests, Institutional, Advisory Board: BMS, MSD, Ipsen, Servier. F. Ghiringhelli: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Amgen, Merck Serono, MSD. T. Vandamme: Financial Interests, Personal, Expert Testimony: MyNeoTx, Eisai, Elmedix; Financial Interests, Personal, Invited Speaker: Nordic Pharma, AstraZeneca, Bayer, Bristol Myers Squibb, Roche, Ipsen, Novartis, Sirtex; Financial Interests, Personal, Advisory Board: SERB, Takeda, Ipsen; Financial Interests, Institutional, Research Grant: Ipsen, Novartis. F. Sclafani: Financial Interests, Personal, Advisory Board: AMAL Therapeutics, Bayer, BMS, Dragonfly Therapeutics, GSK, Nordic Pharma, Roche; Financial Interests, Personal, Invited Speaker: Amgen, Merck, Servier; Financial Interests, Institutional, Research Grant: Amgen, Astellas, AstraZeneca, Bayer, BMS, Merck, MSD, Pierre Fabre, Roche, Sanofi; Non-Financial Interests, Leadership Role, Secretary of the EORTC Gastrointestinal Tract Cancer Group: EORTC Gastrointestinal Tract Cancer Group; Other, Travel grants: Amgen, Bayer, Lilly, Merck, Roche, Servier. All other authors have declared no conflicts of interest.