Background: Profiler 02 (NCT03163732) is a multicentre, randomized molecular screening clinical trial aiming to evaluate the feasibility and the benefit of a large NGS (Next-generation sequencing) panel (FoundationOne Medicine NGS panel or FOne, 324 cancer-related genes) compared to a limited one (Control panel or CTRL, 87 cancer-related genes) in terms of clinical, quality of life and health economic outcomes. We present here the results of the patients with advanced/metastatic sarcoma included in the Profiler 02 trial. Methods: Patients (pts) were enrolled during their first-line of standard therapy for an advanced sarcoma. All sarcomas diagnosIs were performed within the RRePS network (French pathology network of reference for sarcomas) and a central pathological review confirmed if quality and quantity of material were acceptable for molecular analysis. Patients were randomized within the two study arms (FOne versus CTRL) and DNA was analysed using both panels. The primary objective of the study was to compare the proportion of patients for whom a genomically driven recommended therapy (RT) could be initiated based on the FOne versus CTRL panels. A dedicated Molecular Tumour Board (MTB) reviewed tumour genomics data of both panels independently to propose a RT. Results: From January 2018 to July 2019, 39 pts with sarcoma (20F, 19M), with a median age of 54 years [21-81], were randomized between FOne Arm (17 pts) and CTRL Arm (22 pts). Pathological subtypes per arm are presented in the the table. Overall, 19 pts (49%) had at least one genomically driven RT, 11 according to both panels and 8 according to FOne panel exclusively (McNemar’s test, p=0.01). Main RT were CDK4/6 inhibitors (n=5), PI3K/AKT/mTOR inhibitors (n=4), and immunotherapy (n=4). After the MBT, a RT was initiated for seven patients, four according to FOne panel only and three according to both panels. Importantly, a complete response was observed for a metastatic MPNST (Malignant Peripheral Nerve Sheath Tumor) with a high tumour mutational burden (TMB) detected by the FOne panel (37 mutations per megabase) and treated with durvalumab (anti-PDL1) + tremelimumab (anti-CTLA4). Conclusions: Although from an exploratory subgroup analysis, these results suggest that a large molecular profiling panel including TMB (FOne panel) might increase the number of RT and the number of sarcoma patients treated. Studies of precision medicine in rare cancers such as sarcomas are feasible,this approach could benefit to patients. Clinical trial information: NCT03163732.