Colorectal cancer
Conditions
Interventions
A:QL1706 5 mg/kg + bevacizumab 7.5 mg/kg + XELOX every 3 weeks
XELOX <= 8 cycles ? maintenance: QL1706 + bevacizumab + capecitabine (same doses)
All study drugs up to 24 months or until loss of be
Sponsors
The Affiliated Hospital of Qingdao University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Voluntary written informed consent (ICF) must be obtained prior to any study-specific procedures 2. Age >= 18 years and = 3 months 5. Histologically or cytologically confirmed colorectal adenocarcinoma 6. Metastatic colorectal cancer not amenable to curative surgical resection or local therapy 7. No prior systemic anti-tumor therapy for metastatic colorectal adenocarcinoma. For subjects who received prior induction chemotherapy, concurrent chemoradiotherapy, or adjuvant/neoadjuvant chemotherapy, recurrence must occur >= 6 months after completion of the last treatment 8. pMMR (proficient mismatch repair) or MSS (microsatellite stable) status confirmed by genetic testing/immunohistochemistry 9. At least one measurable lesion per RECIST v1.1 that is suitable for repeated and accurate measurement. (Note: Brain metastases cannot serve as target lesions; previously irradiated lesions are not recommended as target lesions. If no other lesions meet target lesion criteria, an irradiated lesion may be considered a target lesion if it is measurable per RECIST v1.1 and there is objective evidence of significant progression post-radiotherapy) 10. Subjects must provide 5-20 unstained FFPE tumor tissue slides from fresh biopsy or archival tissue obtained within 6 months for exploratory biomarker research 11. Adequate organ function as demonstrated by the following laboratory parameters: (1) Absolute neutrophil count (ANC) >= 1.5×10?/L (2) Platelet count >= 100×10?/L (3) Hemoglobin >= 10 g/dL (4) Serum albumin >= 3.0 g/dL (5) Total bilirubin = 60 mL/min (per Cockcroft-Gault formula) (7) International normalized ratio (INR) and activated partial thromboplastin time (APTT) = 1 year, or surgical sterilization or hysterectomy 13. All subjects (male or female) with reproductive potential must use highly effective contraception (failure rate <1% per year) throughout the treatment period and for 120 days after last study drug administration (or 180 days after last chemotherapy administration). Subjects must be able to 14.understand study requirements and comply with study and follow-up procedures
Exclusion criteria
Exclusion criteria: 1. Known MSI-H or dMMR status 2. Other malignancies within 5 years prior to enrollment, except for adequately treated local tumors (e.g., basal cell carcinoma, squamous cell carcinoma of skin, superficial bladder cancer, cervical carcinoma in situ) 3. Prior adjuvant targeted therapy directed against EGFR, VEGF, or VEGFR 4. Prior treatment with any T-cell co-stimulatory or immune checkpoint inhibitors 5. Clinically significant peripheral neuropathy 6. Evidence of bowel obstruction or perforation on clinical/radiological examination, or high risk of perforation/bleeding 7. History of immunodeficiency; current chronic use of systemic corticosteroids or other immunosuppressive agents; active autoimmune disease requiring systemic treatment within past 2 years (excluding hormone replacement therapy, insulin, or physiological corticosteroid replacement) 8. Palliative local therapy for non-target lesions within 2 weeks; therapeutic antibiotics within 2 weeks; non-specific immunomodulatory therapy within 2 weeks; Chinese herbal medicine with anti-tumor indications within 1 week 9. Active or history of inflammatory bowel disease (Crohn's disease, ulcerative colitis, or chronic diarrhea) 10. Active TB, suspected active TB, active syphilis; history of idiopathic pulmonary fibrosis or interstitial pneumonia 11. History of allogeneic organ or hematopoietic stem cell transplantation 12. Severe infection within 4 weeks; active infection requiring systemic anti-infective therapy within 2 weeks (except HBV/HCV antiviral therapy) 13. Active hepatitis B (HBsAg positive with HBV-DNA >1000 copies/mL or above lower limit of detection); active hepatitis C (HCV antibody positive with detectable HCV-RNA) 14. Major surgery within 30 days or planned within 30 days after first dose 15. Active CNS metastases. Treated brain metastases allowed if clinically stable >= 2 weeks and off corticosteroids >= 3 days. Untreated, asymptomatic brain metastases =1.5 cm allowed with monitoring 16. Known brainstem, leptomeningeal, spinal cord metastases or compression 17. Symptomatic pleural/pericardial effusion or ascites requiring repeated drainage 18. Uncontrolled comorbid conditions: decompensated cirrhosis, nephrotic syndrome, uncontrolled metabolic disorders, severe peptic ulcer disease, psychiatric disorders 19. History of myocarditis, cardiomyopathy, malignant arrhythmia; unstable angina/MI/CHF NYHA Class >= 2 within 12 months; esophageal varices, GI perforation, arterial thromboembolism within 6 months; uncontrolled hypertension 20. Bleeding diathesis or coagulopathy; significant bleeding within 1 month; continuous anticoagulation within 10 days 21. Tumor encasing/invading major vessels or organs; risk of esophageal fistula; necrosis/cavitation with bleeding risk 22. Unresolved toxicity from prior anti-cancer therapy >NCI CTCAE v5.0 Grade 1 (except alopecia, platinum-related neurotoxicity) 23. Live vaccine within 30 days or planned during study 24. Known hypersensitivity to study drugs or monoclonal antibodies 25. Psychiatric disorders, drug/alcohol abuse 26. Pregnancy or lactation 27. Any condition that may compromise study compliance or confound results 28. Paraneoplastic syndromes (leukemoid reaction, cachexia >10% weight loss within 3 months) 29. Concurrent participation in interventional clinical trials (observational studies allowed)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1-year PFS rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective response rate, ORR;Disease control rate, DCR;Progression Free Survival, PFS;Overall survival, OS ;Duration of remission, DOR;Conversion Resection Rate (CRR);Safety; | — |
Countries
China
Contacts
Public ContactLv Jing
The Affiliated Hospital of Qingdao University
Outcome results
None listed