TPS3621 Background: A randomized phase II trial, DEEPER (JACCRO CC-13) [NCT02515734], is on-going to evaluate FOLFOXIRI plus cetuximab (cet) vs. FOLFOXIRI plus bevacizumab (bev) in terms of depth of response as primary endpoint in 360 mCRC patients (pts) with RAS wild-type tumors, PS0-1, and no previous chemotherapy. This is a head-to-head comparative trial of 2 key monoclonal antibodies in mCRC treatment; therefore, it would be of interest to perform the biomarker study for developing novel predictors of cet or bev. The clinical utility of circulating tumor DNA (ctDNA) analysis has been largely validated for monitoring during treatment and companion diagnostics after chemotherapy. However, there are few published results regarding ctRNA in cancer treatment. Use of ctRNA from liquid biopsies would enhance tumor profiling through the trending of actionable biomarkers not found in ctDNA, and allow for patient monitoring by measuring dynamic changes in levels of gene expressions. Methods: This study will enroll pts with willing to undergo biopsies of both tissue and blood among participants of the DEEPER trial. The estimated number is 250. The main purpose is to find novel predictors for efficacy of cet or bev in mCRC using liquid biopsies, which are performed to obtain ctDNA and ctRNA at 6 time points: pre-treatment, 8 weeks after treatment start, beginning of maintenance phase in FOLFOXIRI-regimen, progression, before and 8 weeks after 2nd-line treatment. The tissue samples collected before chemotherapy will be used for analyzing intra-tumoral genetic alterations. Associations between analytes in blood/tissue and the clinical outcomes of each treatment (with cet or bev) will be assessed using Fisher’s exact test, Kaplan-Meier curves, and log-rank tests in univariate analyses. We will evaluate on whether transcriptomic analysis in ctRNA could predict treatment efficacy more accurately compared to genomic analysis in ctDNA, and verify the clinical utility of ctRNA testing in mCRC treatment. Accrual will continue until the DEEPER trial is completed. Clinical trial information: UMIN000018412.