P163 An update regarding the meso-ORIGINS study: part of the PREDICT-meso international accelerator network

<h3>Objectives</h3> The PREDICT-Meso International Accelerator Network (&gt;150 investigators, 90 institutions, 16 countries) aims to define the biology driving Pleural Mesothelioma (PM). This requires assembly of a suitably characterised tissue resource spanning asbestos-associated pleural inflammation (AAPI)-to-PM evolution. The Meso-ORIGINS study is delivering this component, incorporating learning from a prior multi-centre feasibility trial where the PM evolution rate was 14% (95%CI 10.5–19.2). The primary objective is to collate longitudinal tissue pairs from patients with AAPI who evolve to PM. Secondary objectives are (a) generation of a multiomic risk prediction model for use in AAPI (b) characterisation of intra-patient tumour heterogeneity using multi-region thoracoscopic biopsies. <h3>Methods</h3> Meso-ORIGINS is a prospective multi-centre observational study, comprising two arms (A, which includes an MRI sub-study, &amp; B). Arm A (target n=300) patients with histologically-confirmed AAPI undergo 6-monthly surveillance for 2 years, with clinical suspicion of PM evolution prompting repeat pleural biopsy and tissue banking. Arm A recruits also have baseline risk profiling via serum proteomics, exhaled breath metabolomics ± perfusion MRI. Arm B (target n=250) patients with suspected PM requiring thoracoscopy have multi-region thoracoscopic biopsies (aim 4–6/case). <h3>Results</h3> Recruitment opened in July 2022 and will end in August 2026. Across 25 UK sites (see figure 1), 408 patients have been recruited: 197/300 (66%) to Arm and 211/250 (84%) to Arm B. 18 PM evolutions (47% target) have been occurred in Arm A, where the current evolution rate is 11.3%, and the 95%CI overlaps with the prior feasibility study (7.3–17.4). 73/211 (35%) and 92/211 (44%) Arm B recruits have been diagnosed with PM and AAPI, respectively. 48/73 (66%) AAPI cases have subsequently been recruited to Arm A, permitting linkage of multi-region pre-PM biopsies. A mean (SD) of 3.9 (1.8) multi-region biopsies have been collected per Arm B case, generating 677 samples. <h3>Conclusions</h3> Meso-ORIGINS is generating a unique longitudinal, multi-region tissue resource spanning AAPI-to-PM evolution. This material is being processed in downstream PREDICT-Meso work-packages focused on multiomic target identification (including WES, spatial transcriptomics) and used for generation of new pre-clinical models and drug screening. Risk profiling results will inform eligibility criteria for future intervention trials for pre-PM patients.