A Clinical Study to Evaluate the Efficacy and Safety of Envafolimab Combined With Cetuxima-βand mFOLFOX6 in Patients With MSS, RAS/BRAF Wild-Type Metastatic Colorectal Cancer (mCRC)

Lab values

• Patients will be excluded from the study if they meet any of the following exclusion criteria:
  • Other malignancies in the past or current (excluding cured basal cell carcinoma or cervical carcinoma in situ).
  • Current duodenal ulcer, ulcerative colitis, intestinal obstruction, or other GI conditions that may cause bleeding or perforation, as judged by the investigator.
  • Patients with symptomatic pleural, peritoneal, or pericardial effusions requiring treatment.
  • History of allergy to monoclonal proteins or any component of the study drugs.
  • Oral traditional Chinese medicine, immunomodulators within 2 weeks, or radiotherapy within 4 weeks before treatment.
  • Thyroid dysfunction that is uncontrolled by medication.
  • Uncontrolled hypertension despite receiving optimal treatment (systolic BP\>150 mmHg or diastolic BP\>90 mmHg).
  • Uncontrolled cardiac conditions: (1) NYHA Class II+ heart failure; (2) unstable angina; (3) myocardial infarction within 1 year; (4) clinically significant arrhythmias requiring treatment.
  • Active autoimmune disease or a history of such diseases.
  • Immunosuppressants, systemic, or absorbable topical steroids for immunosuppression (\>10 mg/day prednisone or equivalent) within 2 weeks before enrollment.
  • CNS metastases.
  • Active infection or unexplained fever\>38.5°C during screening or before first dose (tumor-related fever is acceptable).
  • History or current evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-induced pneumonia, or severe pulmonary dysfunction.
  • Congenital or acquired immunodeficiency, such as HIV infection, or active hepatitis (elevated transaminases not meeting inclusion criteria, HBV DNA≥1000 IU/ml, HCV RNA≥1000 IU/ml).
  • Live vaccine administration within 4 weeks before first dose or planned during the study.
  • History of psychiatric drug abuse, alcoholism, or drug addiction.
  • Pregnant or breastfeeding women, or those planning pregnancy during the trial.
  • Any other factor that may lead to premature study discontinuation, as judged by the investigator.

Other

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• Patients are eligible for the study if they meet all of the following criteria:
  • Prior to enrollment, the participant is required to sign a written informed consent form.
  • Participants should be above 18 years，regardless of gender.
  • Histopathologically confirmed untreated advanced colorectal adenocarcinoma.
  • Tumors with RAS (KRAS, NRAS, HRAS) and BRAF wild-type, MSS phenotype, excluding appendiceal or anal cancer. All listed codons must be wild-type: KRAS: Exons 2, 3, 4 (Codons 12, 13, 59, 61, 117, 146) ; NRAS: Exons 2, 3, 4 (Codons 12, 13, 59, 61, 117, 146)
  • Imaging (enhanced CT/MRI/PET-CT) confirms advanced/metastatic colorectal cancer with measurable lesions according to RECIST v1.1.
  • No prior systemic therapy for advanced/metastatic colorectal cancer, including chemotherapy, EGFR inhibitors (cetuximab, panitumumab), VEGF inhibitors (bevacizumab), and immune checkpoint inhibitors (anti-PD-1/PD-L1/CTLA-4). Adjuvant/neoadjuvant chemotherapy within 6 months before recurrence/metastasis is considered first-line therapy.
  • ECOG PS score 0-1.
  • Expected survival \>12 weeks.
  • Adequate organ function (without blood component or growth factor use within 14 days):
  • Hematology:Neutrophils ≥1.5×10⁹/L, platelets ≥100×10⁹/L, hemoglobin ≥90 g/L. Liver/kidney function: SCr ≤1.5×ULN or creatinine clearance ≥50 ml/min, TBIL ≤1.5×ULN, AST/ALT ≤2.5×ULN (≤5×ULN if due to liver metastasis), urine protein \<2+ (≤1g/24h if ≥2+).
  • Normal coagulation, no active bleeding/thrombosis: INR ≤1.5×ULN, APTT ≤1.5×ULN, PT ≤1.5×ULN.
  • Non-surgically sterile women of childbearing potential must use contraception during and 3 months after treatment; serum/urine HCG negative within 7 days before enrollment; not breastfeeding. Non-surgically sterile men must use contraception with partners during and 3 months after treatment.
  • Willing participant with good compliance for safety and survival follow-up.