Inclusion Criteria:
* 1\. Age ≥18 years and ≤75 years. 2. Good general condition with Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of 0-1.
3\. Histopathologically or cytopathologically confirmed intrahepatic cholangiocarcinoma (ICC).
4\. No prior anti-tumor treatment for intrahepatic cholangiocarcinoma. 5. Confirmed as unresectable, non-ablatable and not eligible for other curative-intent therapies after multidisciplinary discussion by the hepatobiliary tumor expert team of this hospital.
6\. Laboratory test results meet the following criteria (or achievable after short-term medical intervention):
1\. Absolute neutrophil count ≥ 2.0 × 10⁹/L 2. Hemoglobin ≥ 100 g/L 3. Platelet count ≥ 75 × 10⁹/L 4. Plasma albumin ≥ 35 g/L 5. Total serum bilirubin \< 2 × upper limit of normal (ULN) 6. Alanine aminotransferase (ALT) \< 3 × ULN 7. Aspartate aminotransferase (AST) \< 3 × ULN 8. Serum creatinine \< 1.5 × ULN 9. Prothrombin time is normal or no more than 4 seconds above the ULN 10. International normalized ratio (INR) ≤ 2.2 7. Subjects fully understand the study and provide written informed consent. 8. Child-Pugh score ≤ 6 (Child-Pugh A class). 9. At least one measurable lesion per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
10\. For women of child-bearing potential (including non-surgically sterilized subjects): use medically-accepted contraception during study treatment and for 3 months after completion of study treatment; serum or urine human chorionic gonadotropin (HCG) test must be negative within 72 hours prior to enrolment; must not be lactating. For male subjects with female partners of child-bearing potential: effective contraception is required during the study and for 3 months after the last dose of iparomlimab-tuvonralimab.
11\. Expected survival ≥ 12 weeks. 12. No history of autoimmune diseases.
Exclusion Criteria:
* 1\. Severe impairment of major organs including heart, brain, lung or kidney; severe infection or other serious comorbidities (CTCAE v5.0 adverse events ≥ Grade 2) rendering the subject intolerant to study treatment.
2\. History of other malignant neoplasms. 3. History of allergic reactions to relevant study drugs. 4. Known hypersensitivity to any component of iparomlimab-tuvonralimab or to other monoclonal antibody agents.
5\. History of solid-organ transplantation. 6. Prior anti-tumor therapy (including interferon) for ICC. 7. Human immunodeficiency virus (HIV) infection. 8. History of drug abuse or illicit-drug use. 9. Gastrointestinal hemorrhage or cardiovascular/cerebrovascular events within 30 days prior to enrolment.
10\. Pregnant or lactating women; women of child-bearing potential unwilling to adopt contraceptive measures.
11\. Psychiatric disorders that preclude informed consent or proper study participation.
12\. Brain metastases, or bone metastases requiring urgent surgical or radiotherapy intervention.
13\. Active autoimmune disease or relevant medical history (including but not limited to autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism). Note: Subjects with vitiligo; subjects with childhood-onset asthma fully resolved without intervention in adulthood may be enrolled; subjects requiring bronchodilators for asthma are excluded.
14\. Receiving immunosuppressive agents or systemic corticosteroids for immunosuppressive purposes (prednisone \> 10 mg/day or equivalent), and still on such therapy within 2 weeks before enrolment.
15\. Administration of live vaccines within 4 weeks prior to study drug initiation or planned live-vaccine administration during study participation.
16\. Other conditions judged by the investigator to interfere with study conduct or subject safety, such as heavy alcohol consumption, substance abuse, severe comorbid illnesses, marked laboratory abnormalities, or family/social circumstances that may compromise subject safety or protocol compliance.
17\. Clinically significant bleeding episodes or definite bleeding tendency within 3 months before enrolment, e.g. hemoptysis ≥ 2.5 mL, gastrointestinal bleeding, high-risk esophageal-gastric varices, bleeding peptic ulcer, vasculitis. Note: If baseline stool occult blood is positive, repeat testing is required. Persistently positive stool occult blood warrants gastroscopy; subjects with severe esophageal-gastric varices on gastroscopy are excluded. Subjects with gastroscopy performed within the prior 3 months to rule out varices are exempt from repeat gastroscopy.
18\. Uncorrectable coagulopathy or marked hematologic abnormalities with clear bleeding tendency (e.g. hemophilia, coagulation disorders, severe thrombocytopenia).
19\. ECOG-PS score ≥ 2. 20. Child-Pugh score ≥ 7 (Child-Pugh B or C class). 21. Evidence of hepatic decompensation, e.g. massive ascites, history of upper gastrointestinal bleeding due to esophageal-gastric varices within the past year, hepatic encephalopathy or bilirubin encephalopathy.
22\. Uncontrolled hypertension despite antihypertensive medication (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg).
23\. HER2-positive tumor status. 24. Any other conditions that, in the investigator's opinion, may interfere with subject enrolment or endpoint assessment.
