A Randomized, Open-Label, Controlled, Multicenter Phase III Clinical Study of SHR-A1811 in Combination With Chemotherapy and Bevacizumab Versus Standard Therapy as First-Line Treatment for Advanced Colorectal Cancer

A Randomized, Open-label, Controlled, Multicenter Phase III Clinical Study of SHR-A1811 in Combination With mFOLFOX6 (-1) and Bevacizumab Versus mFOLFOX6 in Combination With Bevacizumab as First-line Treatment for Advanced Colorectal Cancer.

This study adopts a randomized, open-label, positive-controlled, multicenter design, aiming to evaluate the efficacy and safety of SHR-A1811 in combination with chemotherapy and bevacizumab versus standard therapy as first-line treatment for advanced colorectal cancer, and to explore the drug's immunogenicity and pharmacokinetic characteristics.

Inclusion Criteria:

1. Subjects voluntarily enroll in the study, sign informed consent, demonstrate good compliance and cooperate with follow-up visits.
2. Aged between 18 and 75 years inclusive, male or female.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
4. Estimated survival expectancy ≥ 12 weeks.
5. Histologically or cytologically confirmed colorectal adenocarcinoma.
6. No prior systemic anti-tumor therapy.
7. Tumor tissue specimen must be provided, either archived within 1 year prior to first study treatment or newly collected fresh specimen.
8. At least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1; the measurable lesion shall not have received prior local therapy such as radiotherapy.
9. Adequate organ function with relevant laboratory tests completed within 7 days before the first study treatment.
10. Male subjects with fertile female partners and fertile female subjects must use highly effective contraception throughout the study. Fertile female subjects must have a negative serum or urine human chorionic gonadotropin (HCG) test within 7 days prior to first study drug administration and shall not be breastfeeding.

Exclusion Criteria:

1. Received systemic anti-tumor therapies (including investigational agents) or major surgery within 4 weeks prior to the first study drug administration; palliative radiotherapy within 2 weeks or surgery within 4 weeks before study treatment initiation.
2. History of hypersensitivity to monoclonal antibodies or any component of the investigational products to be administered in this study.
3. Pre-existing peripheral neuropathy of Grade >1.
4. History of thromboembolic disease within 6 months or hemoptysis within 3 months before first study medication. Subjects with muscular venous thrombosis not requiring anticoagulation per investigator's assessment are eligible for enrollment.
5. CT/MRI evidence of tumor encasement or invasion of major blood vessels.
6. Non-gastrointestinal bleeding within 6 months prior to first study drug administration, or active peptic ulcer disease.
7. Uncontrolled hypertension, or medical history of hypertensive crisis or hypertensive encephalopathy.
8. History of severe cerebrovascular disease.
9. Unresolved toxicities and/or complications from prior interventions that have not recovered to baseline.
10. Subjects with a history of or current leptomeningeal metastases, or active brain metastases.
11. Known or suspected interstitial lung disease (ILD); moderate-to-severe pulmonary disease significantly impairing respiratory function or autoimmune/connective tissue/inflammatory diseases involving the lung within 3 months before first dosing that may interfere with detection or management of drug-related pulmonary toxicity. Subjects who developed ≥Grade 3 ILD during prior immune checkpoint inhibitor treatment are excluded.
12. Symptomatic moderate to severe ascites; uncontrolled moderate or greater pleural or pericardial effusion.
13. Bowel obstruction within 3 months prior to first study treatment, or prior intestinal stent placement with the stent remaining in situ at screening.
14. Uncontrolled or severe cardiovascular disease, or unstable angina/unstable arrhythmia occurring within 1 month before initiation of study treatment.
15. Unexplained fever >38.5°C at screening or prior to first dose; severe infection (CTCAE Grade >2) within 4 weeks before study drug initiation; active pulmonary inflammation on baseline chest imaging, or clinical signs/symptoms of infection requiring oral or intravenous antibiotics within 2 weeks before first dosing.
16. Previous or concurrent diagnosis of other malignant malignancies.
17. Active hepatitis B or active hepatitis C infection.
18. History of immunodeficiency including positive HIV test, congenital/acquired immunodeficiency disorders, or prior solid organ transplantation.
19. Active pulmonary tuberculosis infection within 1 year prior to screening, or prior active pulmonary tuberculosis without standard anti-tuberculosis treatment even if diagnosed more than 1 year ago.
20. Pregnant, breastfeeding females or females planning pregnancy during the study period.
21. Uncontrolled psychiatric disorders, known alcohol abuse, illicit drug dependence, incarceration or other conditions that would preclude completion of study procedures.
22. Any other conditions deemed inappropriate for study participation by the investigator, including clinically significant abnormal laboratory values, familial/social factors or other risks leading to premature study discontinuation or confounding study results.