Neoadjuvant CAPOX Plus Ivonescimab Versus CAPOX for Locally Advanced Colon Cancer

Korábbi kezelés

• Patients who are using immunosuppressants, systemic, or absorbable topical steroids for immunosuppressive purposes (dose >10 mg/day prednisone or equivalent), and continue to use them within 2 weeks before enrollment;
• Previous history of thyroid dysfunction that cannot be maintained within normal range despite medication;
• Use of traditional Chinese medicine immune modulators within 2 weeks before official treatment, or received systemic chemotherapy, immunotherapy, biological therapy, or other anti-tumor treatments including traditional Chinese medicine within 4 weeks prior to enrollment;
• Previous exposure to immunotherapy, including immune checkpoint inhibitors, immune cell therapy, or any treatment targeting tumor immune mechanisms;
• Previous exposure to systemic bevacizumab or its biosimilars;
• Vaccination with live vaccines less than 4 weeks before the start of study medication or likely to occur during the study period;

Más betegség

• History of allergic diseases, severe drug allergies, or known allergy to large molecular weight protein formulations or Ivonesimab;
• Cardiopulmonary insufficiency or hepatic and renal insufficiency that cannot tolerate CAPOX chemotherapy, known allergies to oxaliplatin, capecitabine, irinotecan;
• History of significant bleeding tendency or coagulation disorders;
• Any of the following complications:
  • Major gastrointestinal hemorrhage, perforation
  • Symptomatic cardiac disease (including unstable angina, myocardial infarction, and heart failure)
  • Uncontrolled diabetes and hypertension
  • Uncontrolled diarrhea (despite adequate treatment, it still interferes with daily activities)
• History of uncontrolled cardiac symptoms or diseases;
• Active infection or unexplained fever >38.5°C during screening or before the first dose (patients with fever due to tumor, as determined by the investigator, may be eligible);
• Objective evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-induced pneumonia, active tuberculosis, or severely impaired lung function;
• Congenital or acquired immunodeficiency (such as HIV-infected individuals, HIV 1/2 antibody positive);
• Acute or chronic active hepatitis C (HCV), defined as HCV antibody positive and HCV RNA levels above the limit of detection;
• Known history of psychotropic drug abuse, alcoholism, or drug addiction;

Laborértékek

• For patients with positive acute or chronic active hepatitis B, HBV DNA testing must be performed. If the HBV DNA copy number ≤2×10\^3 copies/mL or ≤400 IU/mL or below the limit of detection, they may enroll. HBsAg (+) patients should receive antiviral therapy throughout the study period to prevent viral reactivation. For patients who are anti-HBc (+), HBsAg (-), anti-HBs (-), and HBV viral load (-), prophylactic antiviral therapy is not required but close monitoring for viral reactivation is necessary;

Egyéb

• Presence of distant metastases;
• Incomplete or complete bowel obstruction; however, patients can be enrolled if the obstruction is relieved by conservative treatment, intestinal stenting, or colostomy;
• Pregnant or breastfeeding women, and men and women unwilling to use contraception.

• Histologically confirmed locally advanced resectable colon adenocarcinoma (colon cancer located more than 12 cm from the anal verge);
• Imaging staging is T4, or T3 (with invasion of the muscularis propria ≥5 mm) combined with at least one of the following risk factors: number of metastatic lymph nodes ≥1, extramural vascular invasion (EMVI+), involvement of the mesocolic fascia. (TNM clinical staging (cTNN) according to the 8th edition of AJCC/UICC guidelines);
• No distant metastasis;
• At least one measurable lesion ;
• Immunohistochemical testing of endoscopic biopsy samples by the study center's pathology department confirms diagnosis as pMMR, or genetic testing confirms MSS/MSS-L status (by PCR or NGS method);
• No prior anti-tumor treatment for colorectal cancer;
• Age ≥18 years and ≤75 years, regardless of gender;
• ECOG performance status score 0-1;
• Signed written informed consent before enrollment;
• Expected survival of more than 12 weeks;
• Adequate organ and bone marrow function.