This study is an open, multi-center, phase II study, aiming to evaluate the safety, tolerability and efficacy of AMT-676 combined with 5-fluorouracil, leucovorin, bevacizumab (or cetuximab) in participants with advanced colorectal cancer, and to assess the PK(Pharmacokinetic) characteristics and immunogenicity of AMT-676.

Inclusion Criteria:

• Patients must be willing and able to sign the ICF, and to adhere to the study visit schedule and other protocol requirements
• Patients with pathologically confirmed, unresectable advanced colorectal adenocarcinoma
• Patients must have at least one measurable lesion as per RECIST version 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Life expectancy ≥6 months
• Patients must have adequate organ function
• Male and female individuals with child bearing potential must agree to take effective contraceptive measures from the moment they sign the informed consent form until 6 months after the last administration of the study drug
• WCBP(Women of Child-Bearing Potential) must have a negative serum pregnancy test within 7 days prior to first dose of the IMP
• Male patients must agree not to donate sperm, and female patients must agree not to donate eggs, while on study treatment and for at least 3 months and 6 months, respectively, after the last dose of the IMP(Investigational Medicinal Product)
• Availability of tumor tissue sample

Exclusion Criteria:

• Prior treatment with any same target
• Systemic anti-neoplastic therapy within five half-lives or 21 days, whichever is shorter, prior to first dose of the IMP
• Persistent toxicities from previous systemic anti-neoplastic treatments of Grade >1
• Major surgery within 28 days prior to first dose of the IMP, or no recovery from side effects of such intervention, or a surgery is planned to be conducted within the expected participation period of the trial or within 4 weeks after the last administration of the drug
• History of thromboembolic or cerebrovascular events during last 6 mouths
• During the three months prior to the first administration of the drug, there were any life-threatening bleeding events, or grade 3 or higher gastrointestinal/venous variceal bleeding events that required blood transfusion, endoscopy, or surgical treatment. Or there were other diseases that the researchers believed posed a higher risk of bleeding or thrombosis during the study period
• Has a history of interstitial lung disease (ILD)/pneumonitis that required steroids, or current ILD/pneumonitis, or suspected ILD/pneumonitis , or other lung disease significantly impacting lung function at baseline.
• Any other concurrent diseases or conditions that could affect the research judgment or impede the completion of the research procedures and follow-up checks
• Central nervous system (CNS) metastasis
• Have a history of active or acute diverticulitis, abdominal abscess, gastrointestinal obstruction, fistula, or peritoneal cancer
• Any evidence indicates severe or uncontrolled systemic diseases
• Acute and/or clinically significant bacterial, fungal or viral infection including hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV).
• Administration of a live vaccine within 28 days prior to the administration of the first dose of the IMP
• Patients requiring concurrent treatment of strong/moderate inhibitors or strong inducers of cytochrome P450 3A4 or 1A2 enzyme (CYP3A or CYP1A2) within 2 weeks prior to the first dose and during the study treatment
• Known or suspected severe allergy/hypersensitivity (resulting in treatment discontinuation) to monoclonal antibodies
• Known or suspected intolerance to the components of the IMP
• Concurrent participation in another investigational therapeutic clinical trial
• Pregnant or breast-feeding females
• Investigator determined that the trial participants who were not suitable to participate in this study for other reasons