QL1706 Plus Bevacizumab for Unresectable or Metastatic MSI-H/dMMR CRC

Inclusion Criteria:

* Voluntarily signs the informed consent form.
* Aged between 18 and 80 years (inclusive) at the time of consent; no gender restriction.
* Histologically confirmed unresectable locally advanced or metastatic colorectal cancer.
* At least one measurable target lesion according to RECIST v1.1.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* No prior immunotherapy for unresectable locally advanced or metastatic colorectal cancer.
* If previously treated with standard neoadjuvant or adjuvant therapy, the interval from the last dose to the first study treatment must be ≥ 6 months.
* Willing and able to provide tumor tissue and blood samples for MSI, RAS, BRAF, and PD-L1 testing.
* Estimated life expectancy of ≥ 12 months.
* Appropriate laboratory values must be met at screening.
* Female participants must be non-lactating, and have a negative pregnancy test result prior to enrollment.
* Participants of childbearing potential must agree to use effective contraception from the time of informed consent until at least 180 days after the last dose of study treatment.

Exclusion Criteria:

* Known history of severe allergic reactions to iparomlimab and tuvonralimab or bevacizumab.
* Active malignancy other than colorectal cancer within 5 years prior to first treatment.
* Large tumor lesions, especially those previously irradiated, with signs of bleeding.
* Imaging showing tumor invasion of major blood vessels (e.g., pulmonary artery or superior vena cava), including encasement or invasion of the vessel lumen.
* Brain metastases (asymptomatic or treated symptomatic brain metastases stable for \>4 weeks allowed).
* Active autoimmune disease requiring systemic treatment.
* Active pulmonary diseases such as tuberculosis, radiation pneumonitis, drug-induced pneumonitis, or severe pulmonary dysfunction during screening.
* Requirement for long-term or high-dose NSAIDs (aspirin \>325 mg) or anticoagulant therapy.
* History of severe gastrointestinal events within 6 months prior to first treatment.
* Severe intestinal obstruction symptoms or signs and unretrieved intestinal stents at screening.
* Cardiovascular or cerebrovascular diseases including but not limited to: NYHA class \> II heart failure; unstable or severe angina; myocardial infarction or stroke within 6 months; atrial fibrillation or other arrhythmias requiring treatment; symptomatic superior vena cava syndrome; prolonged QT interval (male QT \> 450 ms; female QTc \> 470 ms); uncontrolled hypertension despite medication (SBP \>140 mmHg and/or DBP \>90 mmHg) or history of hypertensive crisis or encephalopathy.
* Known bleeding disorders or coagulopathies.
* Uncontrolled pleural, pericardial, or ascitic effusions requiring drainage.
* Active infection or unexplained fever \>38.5°C at screening (cancer-related fever allowed).
* Use of systemic broad-spectrum antibiotics within 30 days prior to first treatment.
* Systemic corticosteroids (\>10 mg prednisone equivalent daily) or immunosuppressants within 14 days prior to first treatment, or immunostimulants within 4 weeks.
* Major surgery, severe fractures, or therapeutic clinical trials within 4 weeks prior to first treatment; herbal treatment within 2 weeks.
* Ongoing adverse events from prior antitumor therapy greater than grade 1.
* HIV infection, other congenital or acquired immunodeficiencies, or history of organ or allogeneic bone marrow transplantation (except corneal transplantation).
* Positive hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (HBcAb) with HBV DNA \>10⁴ copies/mL (\~2000 IU/mL); or positive hepatitis C antibody with HCV RNA \>10³ copies/mL; co-infection with HBV and HCV excluded.
* Vaccination with live or attenuated vaccines within 30 days prior to first treatment.
* Prior treatment with immune checkpoint inhibitors (e.g., anti-PD-1, anti-PD-L1, anti-CTLA-4, anti-OX-40, anti-CD137).
* Prior adjuvant targeted therapy against EGFR, VEGF, or VEGFR (e.g., bevacizumab, cetuximab, panitumumab, apatinib, regorafenib, anlotinib).
* Psychiatric disorders, epilepsy, dementia, or substance abuse that may affect compliance.
* Other conditions or lab abnormalities that may interfere with study participation or confound results as judged by investigators or sponsors.