Study on Sequential Cryoablation, Relaforp Alpha, and Chemotherapy for Bile Duct Tumors

Inclusion criteria

• Age ≥18 years, any gender;
• Histologically confirmed unresectable locally advanced/metastatic intrahepatic cholangiocarcinoma or gallbladder cancer;
• No prior anti-tumor treatment;
• At least one measurable target lesion according to RECIST 1.1 tumor evaluation criteria, and at least one lesion suitable for ablation;
• No active autoimmune disease;
• No concurrent malignancies;
• ECOG performance status 0-1;
• Expected survival ≥ 3 months;
• Adequate organ and bone marrow function (no transfusion, recombinant human thrombopoietin, or colony-stimulating factor treatment within 2 weeks before first dose), defined as:

• Blood count: neutrophils (NEUT) ≥ 1.2×10^9/L; platelets (PLT) ≥ 90×10^9/L; hemoglobin ≥ 90 g/dL;
• Liver function: AST and ALT ≤ 2.5× upper limit of normal (ULN); ALP ≤ 2.5×ULN; total bilirubin (TBIL) ≤ 1.5×ULN; if liver metastases, ALT and AST ≤ 5×ULN;
• INR ≤ 1.25;
• Serum creatinine ≤ 1.5× ULN or creatinine clearance (CrCl) ≥ 30 mL/min (using Cockcroft-Gault formula);
• Female participants of childbearing potential and male participants with partners of childbearing potential must agree to use effective medical contraception from signing the informed consent until 6 months after the last dose;
• Participants voluntarily join the study, sign the informed consent form, and can comply with scheduled visits and related procedures.

Exclusion criteria

• Previously received systemic anti-tumor treatment;
• Active brain metastases; patients with asymptomatic brain metastases can be enrolled; for patients clinically suspected of central nervous system metastasis, a CT or MRI must be performed within 28 days before enrollment to rule out central nervous system metastasis;
• Had other malignant tumors within 5 years before administration (except tumors cured with radical treatment, such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, cervical carcinoma in situ, etc.);
• Allergic to the study drug (Rilafup Alpha Injection, or other immune checkpoint inhibitors);
• History of unstable angina; newly diagnosed angina within 3 months before screening or myocardial infarction within 6 months before screening; arrhythmias (including QTcF: men ≥ 450 ms, women ≥ 470 ms) requiring long-term use of anti-arrhythmic drugs and NYHA class ≥ II heart failure;
• Urinalysis showing protein ≥ and confirmed 24-hour urine protein quantification > 1.0g;
• Infectious pneumonia, non-infectious pneumonia, interstitial pneumonia, or other conditions requiring corticosteroid therapy; history of chronic autoimmune diseases, such as systemic lupus erythematosus; history of ulcerative colitis, Crohn's disease, or other inflammatory bowel diseases; history of chronic diarrhea conditions like irritable bowel syndrome; history of sarcoidosis or tuberculosis; active hepatitis B or C, and HIV infection;
• Currently participating in interventional clinical research treatment, or have received other study drugs or devices within 4 weeks before first administration;
• History of substance abuse that cannot be stopped or mental disorders; Any other situation in which the investigator believes the patient is not suitable for participation in this study.