FMT Combined With Immune Checkpoint Inhibitor and TKI in the Treatment of CRC Patients With Advanced Stage

Inclusion Criteria:

• Sign the informed consent form.
• Metastatic or locally advanced colorectal adenocarcinoma unresectable or unfit forradical radiochemotherapy confirmed by pathology or cytology.
• Microsatellite stable or pMMR patients failed standard treatment, including platinum,irinotecan, fluorouracil and Bevacizumab (Ras and BRAF wt patients should recivedCetuximab).
• Patients have at least one lesion could be evaluated by RECIST v1.1 or mRECIST.
• The Eastern Cooperative Oncology Group (ECOG) performance status score was 0 or 1.
• The life expectancy is more than 3 months.
• Good organ function: Blood routine: hemoglobin ≥90g/L, white blood cell ≥3.0×10^9/L, neutrophil ≥1.5×10^9/L,platelet ≥100×10^9/L; Renal function: creatinine≤1.5×upper limit of normal (UNL) orcreatinine clearance ≥60ml/min; Liver function: total bilirubin (TBIL)≤1.5×upper limit ofnormal (UNL); ALT≤2.5×UNL, AST≤2.5×UNL, ALT≤5×UNL and AST≤5×UNL for patients with livermetastasis.

Exclusion Criteria:

• Have received any anti-PD-1, anti-PD-L1/L2 antibodies, anti-CTLA-4 antibodies andother immunotherapy in the past.
• Have received any TKI therapy in the past.
• Clinically significant ascites.
• Known to have allergic reactions to any ingredients or excipients of experimentaldrugs.
• Have received any antibiotics within 28 days before the first medication or anyprobiotics or prebiotics within 14 days before the first medication.
• Radiotherapy, RFA, interventional therapy or surgery were performed within 28 daysbefore the first medication (except for previous diagnostic biopsy).
• Other active malignant tumors, excluding those who have been disease free for morethan 5 years or in situ cancer considered to have been cured by adequate treatment.
• Brain metastasis or meningeal metastasis has been confirmed. Patients withneurological symptoms should receive brain CT / MRI examination to exclude metastasis.
• Patients who is suffering from intestinal obstruction, gastrointestinal bleeding,pulmonary fibrosis or interstitial pneumonia, renal failure, liver failure orcerebrovascular disease.
• Diabetes was not controlled, defined as HbA1c > 7.5% after anti-diabetic drugs orhypertension was not controlled, defined as systolic / diastolic blood pressure > 140 / 90 mmHg after antihypertensive drug.
• Myocardial infarction, severe/unstable angina, New York Heart Association (NYHA) classIII or IV congestive heart failure in the past 12 months.
• Known to be infected with human immunodeficiency virus (HIV), have acquiredimmunodeficiency syndrome (AIDS) related diseases, have active hepatitis B orhepatitis C.
• Suffering from autoimmune diseases or history of organ transplantation requiringimmunosuppressive therapy.
• May increase the risk associated with participation in the study or administration ofthe study drug or mental illness that may interfere with the interpretation ofresearch results.
• Pregnant women (determined by serum human chorionic gonadotropin [hCG]) or lactatingwomen, or plan to conceive during the treatment period, 2 months after cetuximabtreatment and 6 months after capecitabine treatment. Women of childbearing age withpositive or no pregnancy test at baseline. Women of childbearing age or sexuallyactive men were not willing to use contraception during the study period, at least 2months after cetuximab treatment and 6 months after capecitabine treatment.Postmenopausal women must be amenorrhea for at least 12 months to be consideredinfertile.
• There are other serious diseases that the researchers believe patients cannot beincluded in the study