TARGET National: A U.K.-wide liquid-based molecular profiling program to enhance recruitment to early-phase trials.

TPS3163 Background: Precision medicine programs have largely focused on tissue-based assays to screen patients for genomic variants amenable to experimental targeted therapies. Challenges faced in such studies include time taken to acquire archival biopsies and limitation in capturing tumor heterogeneity and clonal evolution. The TARGET study (Rothwell, Nature Medicine 2019) previously demonstrated feasibility of using ctDNA to match patients to early phase trials with the benefit of rapid turnaround of results. With an ever-increasing number of novel therapies in development targeting rare genomic alterations across different tumor types, ctDNA holds great promise in enhancing recruitment to studies with rapid and efficient comprehensive genomic profiling assays covering a broad range of variants. There is need to perform profiling at scale to identify rare alterations and to utilise networks for identification of suitable clinical trials across the country. ctDNA is not detectable in all patients (owing to differences across disease types/ burden), thus tissue analysis still plays an important role. Methods: TARGET National is an investigator-initiated multi-centre molecular profiling study. The primary endpoints are to establish a national framework to offer profiling from blood samples (or tissue if appropriate) for patients being considered for early phase clinical trials across the UK Experimental Cancer Medicine Centre (ECMC) Network, and to measure the number of patients receiving matched therapy (MT). Secondary endpoints include curating the genomic landscape of the early phase population in the UK, and outcomes for patients receiving MT versus unmatched. Enrolment began in July 2021 and >250 patients have been recruited across 9 ECMCs with plans to expand to 20 centres by Q3 2022. Planned enrolment is 6000 patients over 5 years. Patients must be ≥ 16 years old, provide written consent, have histologically confirmed advanced solid cancer, progressing disease and be considered fit enough to receive an experimental therapy. ctDNA is analysed with Foundation Medicine Liquid CDx with option for other providers. A multi-disciplinary national Molecular Tumor Board enables interpretation of genomic reports and identifies suitable clinical trials, supported by eTARGET; a bespoke clinical-genomic data capture solution including trial finding software. The study provides broad access to genomic profiling throughout the UK, increasing experience with ctDNA assays, and will improve opportunities for patients to participate in early phase research. The UK database will provide means for identification of rare genomic patient groups for new first-in-human studies, and the program provides a national infrastructure to collect additional samples for translational research and pre-clinical models to progress understanding of biological predictors of response and resistance. Clinical trial information: NCT04723316.