2265 - Study Protocol of Neoadjuvant Concurrent Chemoradiotherapy Combined with CAPEOX and Immune Checkpoint Inhibitors for pMMR/MSS T4NanyM0 Colon Cancer: A Phase II, Prospective, Open-Label, Multi-Center, Randomized Controlled Trial(Neo-Color study)

Purpose/Objective(s): For pMMR/MSS locally advanced colon cancer (LACC) patients, the National Comprehensive Cancer Network guidelines recommend systemic therapy as the preferred preoperative approach. Although neoadjuvant chemotherapy can reduce micrometastases, achieve tumor downstaging, and improve R0 resection rates, its efficacy in achieving pathological complete response (pCR) remains limited, less than 5%. The Neo-Color trial investigates a novel preoperative triple-modality strategy (radiotherapy + chemotherapy + immunotherapy) for pMMR/MSS T4 colon cancer, aiming to improve pathological responses and survival.

Materials/Methods: The Neo-Color study is a prospective, open-label, multicenter, randomized controlled phase II clinical trial designed to evaluate the efficacy and safety of concurrent chemoradiotherapy (CCRT) combined with systemic therapy (CAPEOX plus ICIs) as neoadjuvant treatment for patients with pMMR/MSS cT4NanyM0 colon cancer. A total of 108 patients will be randomized 1:1 to experimental and control groups. The experimental group will receive preoperative CCRT combined with one cycle of Iparomlimab and tuvonralimab (QL1706, at the 13th radiotherapy session), followed by 4 cycles of CAPEOX plus QL1706. The control group will receive 4 cycles of CAPEOX chemotherapy. Following the initial treatment regimen, patients will undergo surgery or a watch & wait (W&W) strategy (for patients with clinical complete response (cCR)). The primary endpoint of this study is the complete response rate, defined as the proportion of subjects achieving pCR or cCR. The Neo-Color study aims to provide evidence-based support for incorporating this treatment modality into neoadjuvant treatment guidelines for LACC with pMMR/MSS.

Results: This study will provide evidence for the efficacy and safety of CCRT combined with CAPEOX and ICIs as a neoadjuvant therapy for pMMR/MSS LACC, and it is expected to become a potential candidate treatment option in the future.

Conclusion: Neo-Color study is a prospective, open-label, multicenter, randomized controlled phase II clinical trial, we hypothesize that for patients with pMMR/MSS T4NanyM0 colon cancer, neoadjuvant regimen consisting of CCRT combined with systemic therapy (chemotherapy plus ICIs) will achieve superior short- and long-term outcomes relative to nCT alone.