Nimotuzumab Combined With Trifluridine/Tipiracil in the Treatment of Refractory Metastatic Colorectal Cancer

Inclusion Criteria:

1. Age 18-75 years old, gender unlimited;
2. Histologically or cytologically confirmed diagnosis of colorectal cancer (CRC);
3. Metastatic colorectal cancer, disease progression after previous second-line or above standard therapy;
4. Efficacy of previous line therapy containing an anti-EGFR agent (panitumumab or cetuximab) with complete or partial response, or disease stable; and more than 4 months from last dose of anti-EGFR agent administered before randomization;
5. MSS/pMMR status detected by IHC or PCR;
6. RAS and BRAF wild-type status;
7. ECOG Performance Status 0-1;
8. Measurable disease according to RECIST criteria v1.1;
9. Life expectancy of at least 3 months;
10. Adequate organ and bone marrow function, defined as follows: hemoglobin≥9.0 g/dL; absolute neutrophil count (ANC)≥1.5×10\^9/L; white Blood Cell Count≥4×10\^9/L;platelets≥100×10\^9/L; serum total bilirubin (TBIL)≤1.5×ULN; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times the upper limit of normal (ULN), patients with liver metastases should be ≤ 5 times the ULN; serum creatinine≤1.5×ULN or estimated creatinine clearance \> 60 mL/min;
11. Women of childbearing age should have a negative result of serum HCG or urine pregnancy tests within 72 hours prior to randomization (Postmenopausal women who have had amenorrhea for at least 12 months are considered sterile and women known to have had tubal ligation are not required to undergo pregnancy tests) ;
12. Good compliance and signed informed consent.

Exclusion Criteria:

1. Had other malignancies within the past 5 years or at the same time (exceptions include: cured thyroid cancer, non-melanoma skin cancer, carcinoma in situ of the cervix, stage I ductal carcinoma in situ, stage I endometrial cancer or other solid tumors, and effectively treated lymphoma with no evidence of disease for more than 5 years);
2. Has a serious underlying medical condition that makes it impossible to safely administer the trial treatment. Including but not limited to active infections requiring systemic medication: compensatory heart failure (NYHA grade III and IV), unstable angina, and acute myocardial infarction within 3 months prior to enrollment;
3. Patients who received trifluridine/tipiracil or treated with EGFR monoclonal antibody or EGFR tyrosine kinase inhibitor within four months;
4. Known allergy to prescription or any component of the prescription used in this study;
5. Women who are pregnant or are breastfeeding;
6. Has brain metastases or any symptoms of brain metastases
7. Factors that significantly affect oral drug absorption, such as dysphagia, chronic diarrhea, gastrointestinal obstruction, etc; Uncontrolled Crohn's disease or ulcerative colitis;
8. Participated in other clinical trials within 4 weeks;
9. With HIV, HPV, or syphilis infection, or active hepatitis (hepatitis B, hepatitis C)
10. Other reasons that are not suitable to participate in this study according to the researcher's judgment.