Triple attack on bile duct cancer: chemo, targeted drug, and immunotherapy aim to make the inoperable operable

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * Histologically confirmed intrahepatic cholangiocarcinoma. * Age ≥18 years. * ECOG performance status score of 0 or 1. * Not suitable for radical surgery (including radical hepatic resection, liver transplantation or ablation) after evaluation by the MDT expert group of treating hepatobiliary cancer. Specifically, any of the following conditions are met： 1. R0 resection is not feasible. 2. in subjects without cirrhosis, the volume of normal liver parenchyma is less than 30% of the total volume, or in patients with cirrhosis, the volume of normal liver parenchyma is less than 40% of the total volume, or ICG-R15\>15%. 3. Number of lesions \>1. * No prior systemic anti-tumor treatment for intrahepatic cholangiocarcinoma before the first dose. * According to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST V1.1), at least 1 measurable lesion, or a measurable lesion that has clearly progressed (based on RECIST V1.1 criteria) after local treatment. * Subjects with portal vein tumor thrombus (PVTT): 1. Chen's group A and B, or Cheng's type I-III can be enrolled. 2. Chen's group C, or Cheng's type IV (superior vena cava tumor thrombus) cannot be enrolled. * Subjects with hepatic vein tumor thrombus: 1. VV1 and VV2 types can be enrolled. 2. VV3 type, or Sakamoto type I (inferior vena cava tumor thrombus) can also be enrolled. 3. Sakamoto type II (inferior vena cava tumor thrombus extending above the diaphragm), or Sakamoto type III (inferior vena cava tumor thrombus reaching the right atrium) cannot be enrolled. * Subjects with oligometastases outside the liver can be enrolled: Oligometastases outside the liver are defined as up to three metastatic lesions in a maximum of two organs, with the largest diameter being 3cm. * Child-Pugh score less than or equal to 7. * Adequate organ and bone marrow function, with laboratory test values meeting the following requirements within 7 days prior to inclusion (no blood components, cell growth factors, albumin, or other intravenous or subcutaneous corrective treatment drugs are allowed within 14 days prior to obtaining laboratory tests): 1. Complete blood count: Absolute Neutrophil Count (ANC) ≥1.5×10\^9/L; Platelet count (PLT) ≥75×10\^9/L; Hemoglobin (HGB) ≥9.0 g/dL. 2. Liver function: Total Bilirubin (TBIL) ≤2×Upper Limit of Normal Value (ULN); Alanine Aminotransferase (ALT) and Aspartate Transferase (AST) ≤5×ULN; Serum albumin ≥28 g/L; Alkaline Phosphatase (ALP) ≤5×ULN. 3. Kidney function: Serum Creatinine (Cr) ≤ 1.5×ULN or Clearance of Creatinine (CCr) ≥50mL/min (Cockcroft-Gault formula); Urinalysis shows proteinuria \<2+; For subjects with baseline urinalysis showing proteinuria ≥2+, a 24-hour urine collection should be performed and 24-hour urinary protein quantification \<1g. 4. Coagulation function: International Normalized Ratio (INR) ≤2.3 or Prothrombin Time (PT) extension ≤6 seconds. * Estimated life expectancy of ≥12 weeks. * Female subjects of childbearing age or male subjects whose sexual partners are of childbearing age need to take effective contraceptive measures during the entire treatment period and for 6 months after the last medication. * Signed written informed consent, and able to comply with the visit and related procedures stipulated in the protocol. Exclusion Criteria: * Histologically/cytologically confirmed sarcomatoid intrahepatic cholangiocarcinoma, mixed hepatocellular carcinoma, etc. * History of hepatic encephalopathy or liver transplantation. * Clinically symptomatic pleural effusion, ascites, or pericardial effusion requiring drainage. Patients with only radiologically detected minimal pleural effusion, ascites, or pericardial effusion without symptoms can be included. * Acute or chronic active hepatitis B or C infection, with hepatitis B virus (HBV) DNA \>2000IU/ml or 10\^4 copies/ml; hepatitis C virus (HCV) RNA \>10\^3 copies/ml; co-positive for hepatitis B surface antigen (HbsAg) and anti-HCV antibody. Patients who meet the above criteria after antiviral treatment with nucleoside analogs can be included. * Presence of central nervous system metastases. * History of esophageal or gastric variceal bleeding due to portal hypertension within the past 6 months. Patients assessed by the investigator to be at high risk of bleeding. * Any life-threatening bleeding event within the past 3 months, including those requiring blood transfusion, surgery or local treatment, or continuous drug treatment. * History of arterial or venous thromboembolic events within the past 6 months, including myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or any other serious thromboembolic events. Exceptions are made for thrombosis formation related to implanted venous infusion ports or catheters, or superficial vein thrombosis that has stabilized after routine anticoagulation treatment. Preventive use of low-dose low molecular weight heparin (such as enoxaparin 40 mg/day) is allowed. * Continuous use of aspirin (\>325 mg/day) or other known platelet function inhibitors such as clopidogrel or ticlopidine for 10 days within 2 weeks prior to the first dose. * Uncontrolled hypertension, with systolic blood pressure ≥150mmHg or diastolic blood pressure ≥100mmHg after optimal medical treatment, history of hypertensive crisis or hypertensive encephalopathy. * Presence of any toxicity caused by previous treatment that has not recovered to grade 0 or 1 according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE 5.0) before the first dose of study treatment (excluding alopecia, non-clinically significant and asymptomatic laboratory abnormalities). * Symptomatic congestive heart failure (New York Heart Association class II-IV), left ventricular ejection fraction (LVEF) \<50% as indicated by echocardiography. * Symptomatic or poorly controlled arrhythmia. History of congenital long QT syndrome or corrected QTc \>500 ms (calculated using the Fridericia formula) at screening. * Severe bleeding tendency or coagulation disorder, or currently receiving thrombolytic therapy. * History of gastrointestinal perforation and/or fistula, intestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive intestinal resection (partial colectomy or extensive small bowel resection with chronic diarrhea), Crohn's disease, ulcerative colitis, or chronic diarrhea within the past 6 months. * Received radiotherapy within 3 weeks prior to the first dose of study treatment. For patients who received radiotherapy more than 3 weeks prior to the first dose of study treatment, all of the following conditions must be met for inclusion: no current radiation-related toxicities, no need for corticosteroids, and exclusion of radiation pneumonitis, radiation hepatitis, radiation enteritis, etc. * History or current diagnosis of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, drug-related pneumonia, severe impairment of lung function, and other lung diseases. * Active pulmonary tuberculosis, currently receiving anti-tuberculosis treatment, or received anti-tuberculosis treatment within 1 year prior to the first dose. * Infection with human immunodeficiency virus (HIV) (HIV 1/2 antibody positive), known syphilis infection requiring treatment. * Active or clinically uncontrolled severe infection. Severe infection within 4 weeks prior to the first dose, including but not limited to hospitalization for complications of infection, sepsis, or severe pneumonia. * Active autoimmune disease requiring systemic treatment (such as disease-modifying drugs, corticosteroids, or immunosuppressants) within 2 years prior to the first dose. Replacement therapy (such as thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency, etc.) is allowed. History of primary immunodeficiency. Patients with only autoantibody positivity need to be confirmed by the investigator whether there is an autoimmune disease. * Use of immunosuppressive drugs within 4 weeks prior to the first dose, excluding intranasal, inhaled, or other local corticosteroids or physiological doses of systemic corticosteroids (i.e., no more than 10mg/day prednisone or equivalent doses of other corticosteroids). Temporary use of corticosteroids for the treatment of dyspnea symptoms due to allergies or diseases such as asthma, chronic obstructive pulmonary disease, etc., is allowed. * Received a live attenuated vaccine within 4 weeks prior to the first dose or planned to receive one during the study period. * Major surgery (craniotomy, thoracotomy, or laparotomy) or unhealed wound, ulcer, or fracture within 4 weeks prior to the first dose. Minor surgical procedures or tissue biopsy within 7 days prior to the first dose, excluding venous puncture for the purpose of intravenous infusion, are excluded. * Local treatment for hepatocellular carcinoma within 4 weeks prior to the first dose. * Use of traditional Chinese medicine with anti-tumor indications or drugs with immunomodulatory effects (including thymosin, interferon, interleukin, etc., except for local use to control pleural effusion or ascites, etc.) within 2 weeks prior to the first dose. * Uncontrolled/uncorrectable metabolic disorders or other non-malignant neoplastic organ diseases or systemic diseases or secondary reactions to cancer that could result in higher medical risk and/or uncertainty in survival evaluation, or the presence of other conditions that, in the judgment of the investigator, make enrollment inappropriate. * Diagnosis of other malignancy within 5 years prior to first dose, excluding radically treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or radically resected carcinoma in situ. If other malignancy was diagnosed more than 5 years prior to dosing, even if the liver lesion meets the EASL-ILCA clinical diagnostic criteria for intrahepatic cholangiocarcinoma, the liver lesion must still be diagnosed pathologically or cytologically and those who are definitively intrahepatic cholangiocarcinoma may be enrolled. * Previous treatment with any anti-PD-1 antibody, anti-PD-L1/L2 antibody, anti-CTLA-4 antibody, or other immunotherapy. Previous treatment with targeted therapy against VEGF and/or VEGFR, RAF, MEK, PDGFR, FGFR, etc. * Known allergy to any component of oxaliplatin, 5-fluorouracil, calcium folinate, lenvatinib, or pucotenlimab; or severe allergic reaction to other monoclonal antibodies in the past. * Patients diagnosed with aortic dissection aneurysm, celiac trunk and superior mesenteric artery dissection aneurysm. * Received treatment in other clinical trials within 4 weeks prior to the first dose. * Pregnant or breastfeeding women. * Patients with systemic multiple metastases, portal vein tumor thrombus involving the superior mesenteric vein, inferior vena cava tumor thrombus extending above the diaphragm or reaching the right atrium. * Other acute or chronic diseases, mental illnesses, or laboratory test abnormalities that may result in the following outcomes: increased risk associated with study participation or study drug administration, or interference with the interpretation of study results, and other conditions that, in the investigator's judgment, make the patient ineligible to participate in the study.