FOrMAT: Feasibility of a molecular characterization approach to treatment of patients (pts) with advanced gastrointestinal (GI) tumors.

Abstract

TPS227 Background: The molecular characteristics of a pt’s tumour can determine their suitability for treatment with targeted drugs. Several molecular alterations are only seen in a small percentage of pts and so it is often necessary to screen many pts to identify those who may benefit from targeted therapies. Testing each pt for multiple biomarkers is also increasingly important. Targeted next generation sequencing (NGS) can rapidly interrogate tumours for actionable genetic aberrations and therefore facilitate a personalised treatment approach. FOrMAT aims to assess the feasibility of delivering validated NGS results (to accredited standards) in a clinically meaningful timeframe and how this could be adopted into routine clinical practice in the United Kingdom’s National Health Service. Methods: FOrMAT (ClinicalTrials.gov identifier NCT02112357) is a single-centre translational study in pts with locally advanced/metastatic GI tumours (including gastroesophageal, pancreatic, biliary tract and colorectal). Targeted capture sequencing is performed on archival or fresh biopsy samples to detect mutations, copy number variations and translocations in 45 genes which have prognostic, predictive or pharmacogenomic significance or are targets in current/upcoming clinical trials. Results are discussed by a Sequencing Tumour Board to establish if a pt is potentially suitable for a targeted therapy (e.g. within another clinical trial, as part of standard of care or via a compassionate access program). Changes to pts’ treatment are not mandated. The primary endpoint is the percentage of pts in whom a currently actionable molecular alteration was detected. Secondary endpoints include evaluation of the time required to obtain sequencing results. Blood samples will be collected at baseline and at the time of each tumour response assessment for analysis of molecular markers, including ctDNA and microRNA. Pts may also consent to optional biopsies for exploratory research into tumour heterogeneity and development of pt-derived organoids. The study aims to recruit 200 pts over 2 years. Recruitment started in February 2014 and to date 56 pts have been recruited. Clinical trial information: NCT02112357.