JAGUAR (JACCRO PM-01): A prospective study to evaluate the clinical utility of serial comprehensive genomic profiling testing using circulating tumor DNA in patients with metastatic colorectal cancer.

Abstract

TPS244 Background: Comprehensive genomic profiling (CGP) using next-generation sequencing is recommended in metastatic colorectal cancer (mCRC) to identify actionable alterations. In Japan, CGP is reimbursed only once in a patient’s lifetime and generally after completion of standard systemic therapy, limiting its ability to capture temporal genomic changes. Liquid biopsy using circulating tumor DNA (ctDNA) enables repeated, minimally invasive genomic assessment and may detect emerging or disappearing actionable alterations during the disease course. There have been few prospective studies to assess the frequency and clinical impact of such changes before and after first-line chemotherapy in mCRC. We are therefore conducting a prospective observational study to evaluate the clinical utility of serial CGP testing using ctDNA. Methods: This is a prospective, multicenter observational study conducted at approximately 10 Japanese cancer genomic core and hub hospitals. Eligible patients are adults (≥18 years) with histologically confirmed unresectable mCRC, ECOG performance status 0–1, no prior systemic chemotherapy for metastatic disease, and adequate organ function. Patients undergo ctDNA analysis using the Guardant360 CDx assay at two time points: prior to initiation of first-line chemotherapy and after radiologic confirmation of disease progression on first-line therapy. Results are reviewed by institutional expert panels and returned to patients per local practice, including via telemedicine where applicable. The primary endpoint is the proportion of patients with a change in actionable genomic alterations (defined as OncoKB therapeutic level 1, 2, or R1, excluding variants of unknown significance/synonymous variants) between baseline and post–first-line testing. Secondary endpoints include: proportion of patients with actionable alterations at each time point; proportion with expert panel–recommended therapy and those who receive such therapy; objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) from expert panel–recommended therapy; and feasibility of telemedicine-based result disclosure. Based on prior retrospective data suggesting ~20% change in actionable alterations after systemic therapy, the target sample size is 200 patients, with ≥123 patients expected to have evaluable post–first-line ctDNA results. The study has 90% power at a one-sided α of 0.025 to detect a change proportion ≥15% versus a threshold of 6%. Patient enrollment began in November 2025, with a 12-month accrual period and 18-month follow-up. This trial will clarify the clinical utility of serial ctDNA CGP in mCRC and may support policy change to allow repeated CGP testing during the disease course. Clinical trial information: TBD .