Chidamide+Sintilimab+Bevacizumab Versus Standard Second-Line Therapy of FOLFIRI+Bevacizumab in Subjects With Advanced Microsatellite Stable (MSS/pMMR) Colorectal Cancer Who Have Failed Oxaliplatin-Containing First-Line Therapy
This is a randomized, controlled, multicenter phase Ⅲ study to evaluate the therapeutic efficacy and safety of chidamide + sintilimab + bevacizumab versus standard second-line FOLFIRI + bevacizumab therapy in subjects with advanced microsatellite stable colorectal cancer who have failed first-line oxaliplatin-containing standard therapy. The primary purpose is to compare the progression-free survival (PFS) of chidamide + sintilimab + bevacizumab versus standard second-line FOLFIRI + bevacizumab therapy for colorectal cancer, with a planned enrollment of 176 subjects with advanced microsatellite stable colorectal cancer who have failed first-line oxaliplatin-containing standard therapy.
• Locally advanced unresectable or metastatic colorectal adenocarcinoma (excluding mixed adenosquamous carcinoma and other pathological types) confirmed by pathological histology or cytology.
• Diagnosis of pMMR confirmed by PCR for microsatellite stability (MSS) or low microsatellite instability (MSI-L), or by immunohistochemistry for DNA mismatch repair (MMR) proteins, including MLH1, MSH2, MSH6 and PMS2 protein expression, which result in no protein deletion.
• Patients who have failed first-line oxaliplatin-containing standard therapy and have imaging evidence (e.g., CT scan) or clinical evidence (e.g., cytology report of new ascites or pleural effusion) of disease progression during or after treatment; patients whose intolerance of toxicity has led to discontinuation of first-line oxaliplatin-containing standard therapy may be enrolled; relapse within 180 days after the last dose of oxaliplatin-containing adjuvant therapy.
• There is at least one measurable lesion according to RECIST v1.1.
• ECOG PS score is in the range of 0\
• Subjects who have signed a written informed consent form and who are able to comply with the visits and related procedures specified in the protocol.
• Aged ≥ 18 years old and ≤ 75 years old.
• Expected survival time ≥ 18 weeks.
• Female subjects of childbearing age or male subjects whose sexual partners are at childbearing age are required to take effective contraception measures throughout the treatment period and for 6 months after the treatment (see section 4.3 of the protocol).
⁃ Subjects having adequate organ and bone marrow functions with laboratory test values within 7 days prior to enrollment meeting the following requirements (no blood components, cell growth factors, albumin, and other corrective therapy drugs are allowed to be given within the first 14 days of obtaining laboratory tests), as follows:
‣ 1\) Blood routine: absolute neutrophil count (ANC) ≥ 1.5×109/L; platelet count (PLT) ≥ 100×109/L; hemoglobin level (HGB) ≥ 9.0 g/dL.
‣ 2\) Liver function: serum total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 × ULN in subjects without liver metastases, and ALT and AST ≤ 5.0 × ULN in subjects with liver metastases; serum albumin ≥ 25 g/L.
‣ 3\) Renal function: serum creatinine (Cr) ≤ 1.5 x ULN. 4) Patients with routine urine results showing urine protein \<2+ or routine urine testing showing urine protein ≥ 2+ at baseline should undergo 24-hour urine collection and 24-hour urine protein quantification \< 1 g.
‣ 5\) Coagulation function: international normalized ratio (INR) ≤ 1.5×ULN and activated partial thromboplastin time (APTT) ≤ 1.5×ULN.