xelox +bev +tislelizumab for first-line treatment of mss/pmmr ras-mutated mcrc

Conditions: Tislelizumab; Bevacizumab; Oxaliplatin; Capecitabine; MSS/pMMR; Metastatic Colorectal Cancer (mCRC); RAS-mutated; First-Line

Summary: the goal of this clinical trial is to compare xelox +bev +tislelizumab with standard chemotherapy，in mss/pmmr-type ras-mutated metastatic colorectal adenocarcinoma. the main questions it aims to answer are efficacy and safety of the regimen of xelox +bev +tislelizumab. the investigators want to transform ras-mutated colorectal cancer into a "hot tumor" through the combination of anti-vascular therapy and chemotherapy, and then achieve better therapeutic effect through the combination with immunotherapy. participants will receive the regimen of xelox +bev +tislelizumab.


Eligibility criteria:
inclusion criteria: 1. histologically confirmed initially unresectable mss/pmmr-type ras-mutant metastatic colorectal adenocarcinoma; 2. ecog score of 0 or 1; 3. ability to swallow oral medications; 4. have at least one measurable lesion (according to recist v1.1 standard); 5. no anti-tumor treatment has been received after recurrence and metastasis; 6. neoadjuvant or adjuvant chemotherapy containing fluorouracil drugs is allowed before or after radical resection of colorectal cancer, but the treatment needs to be completed for ≥ 6 months; if oxaliplatin is used in neoadjuvant or adjuvant chemotherapy, it includes the oxaliplatin regimen needs to be completed for ≥12 months; 7. adequate organ function: on the premise of no component blood transfusion within 14 days: white blood cells ≥ 3.5\*10\^9/l and neutrophils ≥ 1.5\*10\^9/l, hemoglobin ≥ 90g/l, platelets ≥ 100\* 10\^9/l; serum bilirubin ≤ 1.5 times the normal value, alanine aminotransferase (alt) ≤ 2.5 times the normal value, aspartate aminotransferase (ast) ≤ 2.5 times the normal value; urinary protein \<2+. or urine protein 2+ but 24-hour urine protein quantity ≤ 1 g; serum creatinine ≤ 1.5 times of normal value, creatinine clearance rate ≥ 60ml/min; doppler ultrasound evaluation: left ventricular ejection fraction (lvef) ≥ lower limit of normal value (50%); 8. expected survival period ≥ 3 months; 9. patients fully understand this research, voluntarily participate in this clinical trial and sign an informed consent; 10. women with reproductive potential (\< 2 years after the last menstrual period) and men use effective contraceptive methods until half a year after the last treatment. exclusion criteria: 1. previously received bevacizumab or anti-ctla4, anti-pd-1/pd-l1 therapeutic antibodies or pathway-targeted drugs; 2. received radiotherapy within 4 weeks before the evaluation; 3. symptomatic peripheral neuropathy \> grade 2 (ctcae5.0 standard); 4. received live vaccine or systemic immune stimulant (including but not limited to interferon or interleukin 2) within 1 month; 5. hiv-positive and other immunodeficiency diseases; 6. active hepatitis b or hepatitis c (except for those who have been infected or cured before, that is, hbsag negative and hepatitis b core antigen anti-hbc antibody positive; except for hepatitis c patients whose hcv rna is negative by pcr); 7. existing autoimmune diseases or other diseases that require immunosuppressant treatment, except for type 1 diabetes; except for hypothyroidism that only requires hormone replacement therapy; skin diseases that do not require systemic treatment (such as vitiligo, psoriasis, alopecia areata); inhaled or topical steroids or equivalent steroids in excess of 10 mg prednisone per day, except for inactive autoimmune disease on adrenal replacement therapy; 8. received systemic hormone therapy or treatment with a daily dose of more than 10 mg prednisone equivalent dose or other forms of immunosuppressive treatment within 7 days, but inhaled or topical steroids or daily application of more than 10 mg prednisone, etc. except for inactive autoimmune diseases treated with adrenal replacement therapy with potent steroids; 9. have a history of organ transplantation; 10. uncontrolled central nervous system (cnc) metastasis (symptomatic or metastatic sites are midbrain, pons, medulla or spinal cord) or other central nervous system diseases; 11. those who have undergone major surgery, open biopsy or obvious traumatic trauma within 1 month, or who may need major surgery during the study period; those who have undergone open biopsy or obvious traumatic trauma, or may need major surgery during the study period; 12. combined with other malignant tumors other than intestinal cancer (except cured basal cell carcinoma or squamous cell carcinoma of the skin and carcinoma in situ of the cervix; the treatment of other malignant tumors has been completed for more than 1 year, and there is no clinical and imaging evidence of recurrence or progression except); 13. combined active and refractory infection; 14. cardiovascular diseases with clinical significance, such as cardiovascular accident (cva) (≤ 6 months before treatment), myocardial infarction (≤ 6 months before treatment), unstable angina, chronic heart failure of nyha ≥ 2 (chf), uncontrolled arrhythmia; uncontrolled hypertension; thromboembolic or bleeding events within 6 months before treatment; 15. evidence of causing coagulation disease; 16. with dysphagia, active peptic ulcer, complete or incomplete intestinal obstruction, active gastrointestinal bleeding, perforation, malabsorption syndrome or uncontrollable gastrointestinal inflammatory disease (such as crohn's disease or ulcerative colon inflammation); 17. severe unhealed wounds/ulcers or severe fractures; 18. any serious acute or chronic medical condition that may affect the patient's participation in the study or interfere with the interpretation of the study results; 19. there are mental illnesses, serious social and psychological illnesses, or researchers believe that there are factors that may affect research compliance; 20. pregnant or lactating women; 21. no therapeutic anticoagulant or antiplatelet drugs or nsaids (aspirin ≤ 325 mg/day allowed); 22. severe allergic reaction to the test drug; 23. reluctance to use alternative therapies such as (but not limited to) bisphosphonates if receiving rankl inhibitors (eg, denosumab).

Keywords: single-arm phase ii