T-CORE2401 trial: A randomized phase II trial of mFOLFOX6 plus cetuximab versus mFOLFOX6 plus bevacizumab as first-line treatment for right-sided, <i>RAS</i> / <i>BRAF</i> wild-type, low-methylated metastatic colon cancer.

Abstract

TPS280 Background: For metastatic colorectal cancer, clinical benefit of anti-EGFR monoclonal antibody (mAb) has been limited to patients (pts) with RAS / BRAF wild-type (wt) left-sided tumors. The role of such therapy for right-sided (RS) metastatic colon cancer remains unclear, particularly in the first-line setting. We previously demonstrated that DNA methylation status (DMS) may influence the efficacy of anti-EGFR mAb + irinotecan in the third-line or later setting: the low-methylated colorectal cancer (LMCC) responded better to anti-EGFR mAbs than high-methylated colorectal cancer (HMCC), irrespective of primary tumor location. We thus hypothesize that even in RS metastatic colon cancer, pts with LMCC may derive greater clinical benefit from anti-EGFR mAb + chemotherapy compared to bevacizumab + chemotherapy in the first-line setting. Methods: The T-CORE2401 is a multicenter, randomized, phase II trial comparing the efficacy and safety of mFOLFOX6 + cetuximab (Cet arm) vs. mFOLFOX6 + bevacizumab (Bev arm) in RAS / BRAF wt RS metastatic colon cancer. Pts will be stratified by DMS determined by OncoGuide EpiLight Methylation Detection Kit (Riken Genesis) into the LMCC or HMCC groups. Key eligibility criteria include: (1) Histologically confirmed unresectable, metastatic adenocarcinoma of the RS colon (cecum to splenic flexure; appendix excluded), (2) No prior systemic chemotherapy, (3) Confirmed RAS / BRAF wt status, (4) ECOG performance status 0–1, (5) Age ≥20 years, and (6) At least one measurable lesion per RECIST v1.1. The primary endpoint is objective response rate (ORR) in the LMCC group. Secondary endpoints include overall survival, progression-free survival, early tumor shrinkage, depth of response, and safety in both LMCC and HMCC groups. Assuming an ORR of 63.6% in the Bev arm, the study is powered to detect an ORR of 81.8% in the Cet arm within the LMCC group (two-sided α = 0.20; β = 0.3), requiring 80 pts (40 per arm) in the LMCC group. The ratio of LMCC to HMCC is expected to be 3:1, and a total of 110 pts will be enrolled. Biomarker analyses will include serial blood sampling and circulating tumor DNA analyses to monitor genomic and epigenomic alterations. Enrollment for the study began in June 2025 (jRCT 1021240067). Clinical trial information: 1021240067 .