safety and efficacy of fruquintinib plus chidamide and sintilimab in the third and later line treatment of mss/pmmr metastatic colorectal cancer

Conditions: Colorectal Cancer Metastatic

Summary: the prognosis of most patients with unresectable locally advanced or metastatic colorectal cancer (crc) remains poor despite the advancements in chemotherapy and target therapy. capability-01 trial investigated the potential efficacy of combining the programmed cell death protein-1 (pd-1) monoclonal antibody sintilimab with the histone deacetylase inhibitor (hdaci) chidamide with or without the anti-vascular endothelial growth factor (vegf) monoclonal antibody bevacizumab in patients with unresectable chemotherapy-refractory locally advanced or metastatic microsatellite stable/proficient mismatch repair (mss/pmmr) colorectal cancer. based on the previous findings of capability-01, we will further evaluate the efficacy and safety of sintilimab and chidamide in combination with fruquintinib in the same setting.


Eligibility criteria:
inclusion criteria: 1. fully understand this study and voluntarily sign the informed consent form; 2. age between 18-75 years inclusive; 3. patients with histologically confirmed unresectable locally advanced, recurrent, or metastatic colorectal adenocarcinoma; 4. failure of standard second-line systemic treatment with measurable lesions; 5. tumor tissue tested for microsatellite stability (mss) or low microsatellite instability (msi-l) by pcr, or confirmed pmmr by immunohistochemistry for dna mismatch repair (mmr) protein (including mlh1, msh2, msh6, and pms2 protein expression); 6. ecog performance status of 0-2, with no deterioration within 7 days; 7. bmi≥18; 8. expected survival ≥3 months; 9. major organ functions meet the following requirements (no use of any blood components and growth factors within 14 days before enrollment): * absolute neutrophil count ≥1.5×109/l, white blood cells ≥4.0×109/l; * platelets ≥100×109/l; * hemoglobin ≥90g/l; * total bilirubin tbil ≤1.5 times uln; * alt and ast ≤5 times uln; * urea/bun and creatinine (cr) ≤1.5×uln (and creatinine clearance (ccr) ≥ 50ml/min); * left ventricular ejection fraction (lvef) ≥50%; * corrected qt interval by fridericia's formula (qtcf) \<470 milliseconds. * inr ≤1.5×uln, aptt ≤1.5×uln. 10. women of childbearing age must use effective contraception; 11. good compliance and cooperation with follow-up. exclusion criteria: 1. unable to comply with the study protocol or procedures; 2. pregnant or breastfeeding women; 3. concurrent with any of the following conditions: uncontrolled hypertension, coronary artery disease, arrhythmias, and heart failure; 4. previous treatment with small molecule tyrosine kinase inhibitors for metastatic disease; 5. previous treatment with romidepsin; 6. previous treatment with immune checkpoint inhibitors for metastatic disease; 7. uncontrollable severe concurrent infections; 8. acute myocardial infarction, acute coronary syndrome, or cabg within 3 months before the first treatment; 9. subjects allergic to the study medication or any of its excipients; 10. known human immunodeficiency virus (hiv) infection. known clinically significant liver disease history, including viral hepatitis \[known carriers of hepatitis b virus (hbv) must exclude active hbv infection, i.e., hbv dna positive (\>1×10\^4 copies/ml or \>2000 iu/ml); known hepatitis c virus (hcv) infection and hcv rna positive (\>1×10\^3 copies/ml)\]; 12. patients whom the investigator deems inappropriate for inclusion in this study.