Cetuximab and Envafolimab Plus mFOLFOXIRI Versus Cetuximab Plus mFOLFOX6/FOLFIRI as First-line Treatment for RAS/BRAF Wild-type, MSS, Unresectable Left-side Metastatic Colorectal Cancer: A Randomized Controlled Phase II Trial (CEIL)
The primary aim of phase II CEIL study is to evaluate the efficacy of cetuximab and envafolimab plus mFOLFOXIRI versus cetuximab plus mFOLFOX6/FOLFIRI as first line treatment of patients with initially unresectable and previously untreated RAS/BRAF wild-type, MSS, left-side metastatic colorectal cancer(mCRC), in terms of Progression-free Survival.
• Signed informed consent obtained before any study specific procedures. Subjects must be able to understand and willing to sign a written informed consent.
• Male or female subjects ≥ 18 years, expected lifespan ≥ 12 weeks.
• Patients have histologically or cytologically confirmed RAS and BRAF wild-type, MSS metastatic colorectal adenocarcinoma (mCRC), excluding appendiceal and anal cancers.
• AJCC/UICC stage IV left-side metastatic colorectal cancer. At least one measurable lesion according to RECIST 1.1.
• The patient has not previously received any systemic treatment specifically targeting advanced or metastatic colorectal cancer, including chemotherapy, monoclonal antibodies such as cetuximab or panitumumab targeting the epidermal growth factor receptor (EGFR), bevacizumab targeting the vascular endothelial growth factor (VEGF), immune checkpoint inhibitors such as anti-PD-1 or anti-PD-L1 antibodies, and anti-CTLA-4 antibodies. If recurrence or metastasis occurs during or within 6 months after adjuvant or neoadjuvant chemotherapy, adjuvant/neoadjuvant therapy is considered as a first-line systemic treatment for advanced or metastatic disease.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Within 7 days before treatment, the following laboratory test values are obtained and appropriate organ function is present:
⁃ Hemoglobin ≥ 90g/L, neutrophil count ≥ 1.5 × 10\^9/L, platelet count ≥ 75 × 10\^9/L; Serum total bilirubin ≤ 1.5 × upper limit of normal (UNL); Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 × UNL; if there are liver metastases, AST or ALT ≤ 5 × UNL; Serum creatinine ≤ 1.5 × UNL.
• Women of childbearing potential must have a negative blood pregnancy test at the baseline visit. For this trial, women of childbearing potential are defined as all women after puberty, unless they are postmenopausal for at least 12 continuous months, are surgically sterile, or are sexually inactive.
• Patients are not allowed to participate in other clinical trials during the study period and willing to comply with the study protocol and visit plan.