This is a single-arm, multicenter, phase II clinical trial evaluating the safety and efficacy of neoadjuvant encorafenib plus cetuximab N01 and mFOLFOX6 in patients with locally advanced BRAF V600E-mutated colorectal cancer, with or without resectable metastases. Eligible patients will receive 8 weeks of neoadjuvant treatment with encorafenib, cetuximab N01, and mFOLFOX6, followed by tumor response assessment and radical surgery when appropriate. The primary endpoint is 18-month disease-free survival (DFS). Secondary endpoints include perioperative safety, objective response rate, pathological response rate, 1-year DFS, 3-year DFS, overall safety, and quality of life. This study aims to explore whether incorporating BRAF and EGFR targeted therapy into standard chemotherapy in the neoadjuvant setting can improve tumor control and long-term outcomes in this high-risk molecular subgroup of colorectal cancer.
The subjects voluntarily joined this study, signed an informed consent form, and showed good compliance;
Age: 18-75 years old, PS score 0-1;
Colorectal adenocarcinoma diagnosed by histopathology, preoperative staging: T4N0-2M0, T3N2M0, T0-4N0-2M1a (with metastatic lesions present, requiring MDT evaluation as resectable); PMMR/MSS, BRAF V600E mutation, and both NRAS and KRAS wild-type;
Locally advanced colorectal cancer requires initial diagnosis of patients who have not received systematic treatment in the past. Patients with resectable metastatic lesions are required to have not received targeted therapy in the past, and new metastases after adjuvant therapy can be included in this study.
Patients with MSI-H/dMMR present;
Patients with multiple metastases that cannot be resected;
Has had or is currently suffering from other malignant tumors within the past 3 years. The following situations can be included in the group:Cured cervical carcinoma in situ, non melanoma skin cancer, and superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ), and T1 (tumor infiltrating basement membrane)];
Patients with active inflammatory bowel disease within the first 4 weeks of enrollment;
Single group
Neoadjuvant therapy of encorafenib plus cetuximab N01 and mFOLFOX6
DrugEligible subjects will receive neoadjuvant therapy comprising mFOLFOX6 (oxalipatin 130mg/m², IV + 5-Fu 2400 mg/m², IV, q2w), encorafenib (300mg, qd, po, d1-28) and cetuximab N01 (500 mg/m², IV, q2w) for two months
18-month disease-free survival rate
the proportion of participants who are alive and free of disease recurrence or metastasis at 18 months after randomization
objective response rate
the proportion of participants with a best overall response of either CR or PR
1-year disease-free survival rate
the proportion of participants who are alive and free of disease recurrence or metastasis at 1 year after randomization
3-year disease-free survival rate
the proportion of participants who are alive and free of disease recurrence or metastasis at 3 years after randomization
major pathological response rate
proportion of patients who achieve a major pathological response (10% or less viable tumor remaining in the resected tumor specimen after neoadjuvant treatment) after neoadjuvant treatment.
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Zhejiang University
Lead sponsor
Second Affiliated Hospital, Zhejiang University, School of Medicine
Sponsor institution
