HAIC Plus QL1706 & Bevacizumab in Unresectable HER2-Negative ICC

Laborértékek

• 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.
  • 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.
  • 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.
  • Pregnant or lactating women; women of child-bearing potential unwilling to adopt contraceptive measures.
  • Psychiatric disorders that preclude informed consent or proper study participation.
  • Brain metastases, or bone metastases requiring urgent surgical or radiotherapy intervention.
  • 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.
  • 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.
  • Administration of live vaccines within 4 weeks prior to study drug initiation or planned live-vaccine administration during study participation.
  • 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.
  • 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.
  • Uncorrectable coagulopathy or marked hematologic abnormalities with clear bleeding tendency (e.g. hemophilia, coagulation disorders, severe thrombocytopenia).
  • 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.
  • Uncontrolled hypertension despite antihypertensive medication (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg).
  • HER2-positive tumor status. 24. Any other conditions that, in the investigator's opinion, may interfere with subject enrolment or endpoint assessment.

• 1. Age ≥18 years and ≤75 years. 2. Good general condition with Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of 0-1.
  • Histopathologically or cytopathologically confirmed intrahepatic cholangiocarcinoma (ICC).
  • 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.
  • Laboratory test results meet the following criteria (or achievable after short-term medical intervention):
  • 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).
  • 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.
  • Expected survival ≥ 12 weeks. 12. No history of autoimmune diseases.