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 abovestandard therapy;
4. Efficacy of previous line therapy containing an anti-EGFR agent (panitumumab orcetuximab) with complete or partial response, or disease stable; and more than 4months 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 CellCount≥4×10^9/L;platelets≥100×10^9/L; serum total bilirubin (TBIL)≤1.5×ULN; aspartateaminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times the upper limitof normal (ULN), patients with liver metastases should be ≤ 5 times the ULN; serumcreatinine≤1.5×ULN or estimated creatinine clearance > 60 mL/min;
11. Women of childbearing age should have a negative result of serum HCG or urinepregnancy tests within 72 hours prior to randomization (Postmenopausal women who havehad amenorrhea for at least 12 months are considered sterile and women known to havehad 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 (exceptionsinclude: cured thyroid cancer, non-melanoma skin cancer, carcinoma in situ of thecervix, stage I ductal carcinoma in situ, stage I endometrial cancer or other solidtumors, and effectively treated lymphoma with no evidence of disease for more than 5years);
2. Has a serious underlying medical condition that makes it impossible to safelyadminister the trial treatment. Including but not limited to active infectionsrequiring 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 antibodyor 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, chronicdiarrhea, gastrointestinal obstruction, etc; Uncontrolled Crohn's disease orulcerative 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 theresearcher's judgment.