This study aims to evaluate the safety and preliminary efficacy of anlotinib combined with cadonilimab and PULSAR in previously treated advanced unresectable or netastatic biliary tract cancer.

Inclusion Criteria:

• Age: 18-75 years, regardless of gender.
• Histopathologically confirmed diagnosis of biliary tract cancer (BTC).
• Patients with unresectable or metastatic BTC who have progressed after at least one line of standard systemic therapy
• At least one measurable lesion (RECIST v1.1) not previously irradiated.
• ECOG Performance Status (PS): 0-1.
• Expected survival ≥ 3 months.
• Willing and able to comply with study procedures, treatment, and follow-up.
• No contraindications to radiotherapy.
• Adequate organ function: WBC ≥ 2.5×10⁹/L, ANC ≥ 1.5×10⁹/L; PLT ≥ 75×10⁹/L; Hemoglobin (HGB) ≥ 90 g/L (no transfusion or EPO dependence within 7 days); Total bilirubin (Tbil) ≤ 1.5×ULN; ALT/AST ≤ 5×ULN;Albumin ≥ 30 g/L; INR ≤ 1.5×ULN; Serum creatinine (Cr) ≤ 1.5×ULN;Urine protein ≤ 1+
• Prior immunotherapy must have been discontinued for at least 4 weeks (to avoid cross-reactivity).
• Voluntary participation with signed informed consent form.

Exclusion Criteria:

• History of severe allergic reactions to chimeric, human, or humanized antibodies, or fusion proteins.
• Pregnant or lactating women; men or women of childbearing potential who are unwilling or unable to use effective contraception.
• History of other malignancies within the past 5 years, except for: malignancies treated with curative intent with no known active disease for ≥ 5 years prior to first dose and with low potential risk of recurrence; adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; adequately treated carcinoma in situ without evidence of disease.
• Clinically symptomatic moderate to large volume pleural or peritoneal effusion.
• Active bleeding or coagulopathy (PT > 16 s, APTT > 43 s, INR > 1.5 × ULN), bleeding tendency, or ongoing thrombolytic, anticoagulant, or antiplatelet therapy.
• History of gastrointestinal bleeding within the past 6 months, or clear evidence of gastrointestinal bleeding tendency, such as: known active localized ulcerative lesions, fecal occult blood ≥ 2+ (patients with persistent fecal occult blood 1+ should undergo gastroscopy).
• Severe gastric or esophageal varices requiring interventional treatment.
• Untreated active hepatitis B. (Note: Subjects with hepatitis B who are receiving antiviral therapy and have HBV viral load < 2000 IU/mL may be permitted to participate in the study.)
• Active hepatitis C, defined as positive anti-HCV antibody or positive HCV-RNA with abnormal liver function.
• History of psychoactive substance abuse that cannot be discontinued, or history of psychiatric disorders.
• History of solid organ or bone marrow transplantation, or active autoimmune disease requiring systemic treatment within 2 years prior to first dose.
• Known immunodeficiency disease or HIV infection.
• Objective evidence of past or current pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonitis, or severely impaired lung function.
• Major surgery (e.g., hepatic or other site) within 4 weeks prior to first dose, or minor surgery (e.g., simple excision, tooth extraction) within 1 week prior to first dose.
• Receipt of vaccination within 30 days prior to first dose.
• Occurrence of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks prior to first dose.
• Any clinically significant laboratory or physical abnormality that, in the investigator's opinion, may affect safety evaluation, such as: active infection requiring systemic treatment, uncontrolled diabetes, hypertension that cannot be controlled to within normal range (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg) after treatment with ≤ 2 antihypertensive drugs, myocardial infarction within the past 6 months, thyroid dysfunction ( > NCI CTCAE v5.0 Grade 1), etc.
• Any other condition that the investigator considers inappropriate for enrollment.

IPD will not be shared in order to protect participant confidentiality, in compliance with local data protection regulations and ethical committee requirements. Additionally, IPD sharing is restricted under contractual agreements with study sponsors/partners, who retain data ownership for independent analyses. Given the complexity and size of the dataset (e.g., genomic/imaging data), anonymized IPD sharing is technically unfeasible without risking data integrity. Furthermore, to safeguard intellectual property rights and permit ongoing secondary analyses by the research team, IPD will be retained internally.