Peter van Mourik

173 Rationale of the HIT-CF Organoid study mutation by PCR-DNA sequencing of the patient derived organoids for the subsequent clinical trial. Organoid biobanking for future use The organoids generated will be stored by HUB for the duration of the study. During the HIT-CF project, a new biobank is being created to store the organoids for future use and make them available to researchers worldwide. Ethical experts will interview stakeholders and CF patients in order to explore the optimal governance of the biobank, and to generate an informed consent form that covers all aspects of this biobank. Once this new biobank has been set up, patients will be asked to sign informed consent for permission to use their organoids in this biobank. This will only occur if the local study site has ethical approval for the separate biobank. If patients refuse, the organoids will be destroyed after the HIT-CF Organoid Study. If patients sign the informed consent, their organoids will enter the organoid biobank. DISCUSSION The HIT-CF Organoid Study applies intestinal organoids for personalized medicine in cystic fibrosis. Rare genetic variants of cystic fibrosis are currently excluded in CFTR- modulator trials, while it is expected that some of these variants are very responsive to treatment. By generating patient-specific organoids for these rare genotypes, a functional assessment of drug response per individual can be generated and treatment can be tailored to the individual. With the accompanying subsequent clinical trials, an innovative opportunity is created for CF-patients with rare mutations to get access to new CFTR-modulator drugs. Personalized medicine approaches using organoids are ongoing in several diseases, but are still limited in scale. Several oncological trials are being conducted, such as in lung (clinicaltrials.gov identifier NCT03979170), breast (NCT03544047) and pancreatic cancer (NCT03544255). However, these studies are single-centre and aim to retrospectively compare in vivo and in vitro treatment responses. In the field of cystic fibrosis, pilot studies found that organoids can identify individuals that clinically benefit from the CFTR-modulating drugs ivacaftor and lumacaftor/ ivacaftor with high accuracy, but these studies had a limited sample size 26,27 . By including up to 500 subjects in sites across Europe and performing confirmatory clinical trials, our project will be the first to prospectively assess the feasibility of using organoids for personalized medicine on such a large scale. One of the strengths of 8