Anlotinib+Cadonilimab+PULSAR in Advanced Biliary Tract Cancer

Korábbi kezelés

• 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.)
• History of solid organ or bone marrow transplantation, or active autoimmune disease requiring systemic treatment within 2 years prior to first dose.
• 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.

Más betegség

• History of severe allergic reactions to chimeric, human, or humanized antibodies, or fusion proteins.
• 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).
• 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.
• 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.
• Any other condition that the investigator considers inappropriate for enrollment.

Laborértékek

• Active bleeding or coagulopathy (PT \> 16 s, APTT \> 43 s, INR \> 1.5 × ULN), bleeding tendency, or ongoing thrombolytic, anticoagulant, or antiplatelet therapy.
• 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.

Életkor

• 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.

Egyéb

• Pregnant or lactating women; men or women of childbearing potential who are unwilling or unable to use effective contraception.
• Clinically symptomatic moderate to large volume pleural or peritoneal effusion.
• Severe gastric or esophageal varices requiring interventional treatment.

• 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.