Anlotinib Combined With Sintilimab as First-line Treatment for Advanced Non-liver Metastatic Colorectal Cancer

Inclusion criteria

• Patients with histologically or cytologically confirmed advanced colorectal adenocarcinoma.
• Patients with non-hepatic metastases who explicitly refuse chemotherapy.
• Patients who have not received prior systemic therapy, or those with metastasis or recurrence occurring ≥12 months after completion of adjuvant therapy.
• At least one measurable lesion according to RECIST 1.1 criteria.
• Prior local radiotherapy is permitted if completed at least 3 weeks before the first study drug administration; however, lesions used for RECIST evaluation must be outside the radiation field.
• Age ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy ≥12 weeks.
• Ability to understand and voluntarily provide written informed consent.
• For women of childbearing potential, a negative pregnancy test within 7 days prior to treatment initiation. Both patients and their partners must agree to use effective contraception during the study period.

Exclusion criteria

• Patients who have undergone major surgery or sustained severe trauma within 4 weeks prior to the first dose of the study drug.
• Patients with a history of hypersensitivity to any component of the study regimen.
• Patients who are planning to conceive, are pregnant.
• Patients with brain metastases who are unable to accurately describe their symptoms or condition.
• Patients with a history of autoimmune diseases or organ transplantation.
• Use of immunosuppressive medications within 2 weeks prior to the initiation of study treatment (excluding inhaled corticosteroids, or physiological replacement doses of steroids equivalent to ≤10 mg/day of prednisone).
• Administration of a live attenuated vaccine within 4 weeks prior to the start of study treatment or planned vaccination during the study period.
• Prior treatment with anlotinib, anti-PD-1/PD-L1 monoclonal antibodies, or any other therapy targeting T-cell co-stimulation or immune checkpoint pathways.
• History of any of the following within 6 months before starting study treatment: myocardial infarction, severe/unstable angina, congestive heart failure of New York Heart Association (NYHA) Class 2 or higher, or poorly controlled cardiac arrhythmias.
• Laboratory test abnormalities meeting any of the following criteria:

• Absolute neutrophil count (ANC) <1,500/mm³.
• Platelet count <75,000/mm³.
• Total bilirubin >1.5 times the upper limit of normal (ULN).
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >2.5 times ULN.
• Serum creatinine >1.5 times ULN.
• Diagnosis of any malignancy other than advanced colorectal cancer within the 5 years preceding the start of study treatment, except for carcinoma in situ of the cervix, cured basal cell carcinoma, or bladder epithelial tumors.
• Patients with colorectal cancer amenable to curative surgical resection (however, those who explicitly refuse surgery or are deemed unsuitable for surgery may be eligible).
• History of substance abuse, drug use, or alcohol dependence.
• Lack of legal capacity or limited civil capacity.
• Any other condition that, in the opinion of the Investigator, makes the patient unsuitable for study participation.