Efficacy and Safety Study of Thymalfasin in Combination with Targeted Immunotherapy (Regorafenib and Tislelizumab) in Patients with Advanced PMMR/MSS Colorectal Cancer Who Failed Standard of Care: a Multicenter, Open-label, Randomized, Controlled Clinical Study
This is a multicenter, open-label, prospective, randomized controlled Phase II clinical study. All eligible subjects will be randomly assigned in a 1:1 ratio to either the triple therapy group or the double therapy group. Triple therapy group: Subjects will receive Thymalfasin in combination with Regorafenib and Tislelizumab until iCPD is achieved per iRECIST (progressive disease (PD) per iRECIST), or until an intolerable toxicity occurs; Double therapy group: Subjects will receive Regorafenib and Tislelizumab until iCPD is achieved per iRECIST (PD per iRECIST), or until an intolerable toxicity occurs.
• Able to sign a written informed consent form (ICF) and able to understand and comply with the requirements of this study Male or female aged 18 to 75 Histologically or cytologically confirmed advanced or metastatic colorectal adenocarcinoma Mismatch repair (MMR) protein expression or microsatellite instability (MSI) testing showing pMMR/MSS ECOG score of 0 or 1 At least one measurable lesion per iRECIST Expected survival of ≥ 3 months Disease progression or intolerance after at least second-line standard systemic therapy
⁃ Normal major organ function and hematological parameters (within 14 days prior to randomization):
⁃ Hematology tests must meet the following criteria:
⁃ WBCs≥2.0×10\^9/L NEUT≥1.5×10\^9/L Hb≥90g/L (9.0g/dL); PLT ≥100×10\^9/L;
⁃ Biochemistry tests must meet the following criteria:
⁃ TBIL ≤ 1.5 × upper limit of normal (ULN); Without liver metastases, ALT or AST ≤ 3.0 ULN; with liver metastases, ALT or AST ≤ 5 ULN; Serum albumin level ≥ 30 g/L Serum Cr ≤ 1.5 ULN, with an endogenous creatinine clearance (CrCl) \> 40 mL/min (using Cockcroft-Gault formula) For females: CrCl =((140-Age）×Weight（kg）× 0.85)/(72 × Cr (mg/dL)) For males: CrCl =((140-Age）×Weight（kg）× 1.00)/(72 × Cr (mg/dL)) Urine protein \< 2+; if urine protein ≥ 2+, 24-hour urine protein must be \< 1 g Prothrombin time or activated partial thromboplastin time and international normalized ratio ≤ 1.5 × ULN Able to swallow and absorb oral medication Females of childbearing potential must use appropriate contraceptive methods during the study and for 6 months after the last dose of the study drug. For males, they should be surgically sterilized or agree to use appropriate contraceptive methods during the study and for 6 months after the last dose of the study drug.