Exploring Sintilimab + Bevacizumab + Decitabine for Advanced pMMR/MSS Colorectal Cancer (After 2+ Prior Therapies）

Inclusion Criteria:

1. Signed written informed consent obtained prior to initiation of any trial-related procedures;
2. Age ≥18 years;
3. Histologically confirmed colorectal adenocarcinoma;
4. Microsatellite stable (MSS), microsatellite instability-low (MSI-L), or proficient mismatch repair (pMMR) status;
5. ECOG Performance Status (PS) score of 0-1;
6. Documented disease progression following standard second-line systemic therapy (prior exposure to irinotecan, oxaliplatin, or fluorouracil-based regimens, with or without targeted therapy \[e.g., bevacizumab, cetuximab\]);
7. Adequate organ and bone marrow function confirmed by laboratory parameters.
8. Anticipated survival exceeding 3 months.
9. For females of childbearing potential, a negative urine or serum pregnancy test must be confirmed within 3 days prior to the first dose of study drug (Cycle 1 Day 1). Serum pregnancy testing is required if urine results are inconclusive. Non-childbearing potential is defined as ≥1 year postmenopausal, surgically sterilized (bilateral oophorectomy or hysterectomy), or confirmed premature ovarian failure.
10. All subjects at risk of conception must employ highly effective contraception (failure rate \<1% per year) throughout the treatment period and for 120 days after the last dose of study drug.
11. Subjects must consent to provide sufficient tumor tissue specimens for PD-L1 expression analysis, including archived samples (paraffin-embedded blocks or unstained sections meeting protocol-specified requirements). If archived tissue is unavailable, subjects must agree to undergo re-biopsy of the tumor lesion.

Exclusion Criteria:

1. Other malignancies diagnosed within the past 5 years, excluding radically resected basal cell or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix.
2. Microsatellite instability-high (MSI-H) or deficient DNA mismatch repair (dMMR).
3. Current participation in interventional clinical trials or administration of investigational drugs/devices within 4 weeks prior to the first dose.
4. Prior therapy with anti-PD-1/PD-L1/PD-L2 agents or drugs targeting stimulatory/coinhibitory T-cell receptors (e.g., CTLA-4, OX-40, CD137).
5. Active autoimmune disease requiring systemic treatment (e.g., disease-modifying agents, corticosteroids, or immunosuppressants) within 2 years prior to the first dose. Exemptions: Replacement therapy (e.g., thyroxine, insulin, or physiologic glucocorticoids for adrenal/pituitary insufficiency).
6. Radiographic evidence of tumor invasion/encasement of major blood vessels or bleeding tendency assessed by investigators/radiologists.
7. Major surgery within 4 weeks prior to the first dose (excluding biopsy) or anticipated major surgery during the study period.
8. Non-healed wounds, ulcers, or fractures.
9. Minor surgical procedures (requiring local anesthesia, e.g., central venous catheterization) within 48 hours prior to the first dose.
10. Current or recent (within 10 days prior to the first dose) daily use of aspirin (\>325 mg/day) or other NSAIDs with platelet-inhibiting effects.
11. Current or recent (within 10 days prior to the first dose) full-dose anticoagulants/thrombolytics (prophylactic low-dose anticoagulants permitted: ≤1 mg/day warfarin \[INR ≤1.5\], ≤12,000 U/day heparin, or ≤100 mg/day aspirin).
12. Inherited bleeding diathesis, coagulation disorders, or history of thrombosis.
13. History of allogeneic organ transplantation (excluding corneal transplants) or allogeneic hematopoietic stem cell transplantation.
14. Known hypersensitivity to sintilimab, bevacizumab, decitabine, or their excipients.
15. Inadequate recovery from prior intervention-related toxicities/complications (i.e., \>Grade 1 or not returned to baseline, excluding fatigue/alopecia).
16. HIV infection (HIV 1/2 antibody-positive).
17. Untreated active hepatitis B (HBsAg-positive with HBV-DNA exceeding the upper limit of normal).
18. Pregnancy or lactation.
19. Severe or uncontrolled systemic diseases.
20. Any condition (medical, psychiatric, laboratory abnormality, or logistical) that, in the investigator's judgment, compromises patient safety, data integrity, or protocol compliance.