Precision Integrated Strategies and Efficacy Evaluation for Biliary Tract Cancers: An Umbrella Platform Study

This study is a prospective, multicenter, open-label, umbrella phase II clinical trial. Based on different multigene expression profiling subtypes and potential molecular characteristics of various pathways, 8 treatment arms and 13 treatment groups are preliminarily designed. After successful screening, investigators will assign eligible subjects to a treatment group based on the patient's genetic test report (if available) and performance status. For subjects without a genetic test report, they will be allocated to Arm H to receive immunotherapy combined with chemotherapy or other regimens. The mutations involved include the following: A: FGFR, B: IDH1, C: KRAS, D: NTRK, E: BRAF V600E, F: BRCA1/2, G: HER2, and H: pan-negative. Additional corresponding targets may be added later based on clinical practice.

Inclusion criteria

• The patient voluntarily joins this study and signs the informed consent form.
• Age: ≥18 years, male or female.
• Histologically or cytologically confirmed advanced biliary tract malignancies, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer.
• No prior systemic therapy for advanced BTC (biliary tract cancer).
• At least one measurable lesion as per RECIST v1.1 (spiral CT scan long diameter ≥10 mm or short diameter of enlarged lymph node ≥15 mm; lesions previously treated with local therapy may be considered target lesions only after documented progression according to RECIST v1.1).
• ECOG performance status: 0-1.
• Expected survival ≥12 weeks.
• Adequate major organ function.
• Female subjects of childbearing potential must have a negative pregnancy test (serum or urine) within 7 days before the first dose, must not be breastfeeding, and must voluntarily agree to use effective contraceptive measures during the study period and for 6 months after the last dose of chemotherapy. For male subjects with a female partner of childbearing potential, they must be surgically sterile or agree to use effective contraceptive measures during the study period and for 3 months after the last dose of chemotherapy; sperm donation is not allowed during the study.
• Subjects are expected to have good compliance and be able to follow the protocol requirements for efficacy and adverse event follow-up.

Exclusion criteria

• Has another active malignancy other than BTC within 5 years or concurrently.
• Has poorly controlled cardiac clinical symptoms or diseases.
• Has hypertension that cannot be reduced to normal range with antihypertensive medication; has a history of hypertensive crisis or hypertensive encephalopathy.
• Any clinically significant gastrointestinal disorders, including bleeding, inflammation, obstruction, or diarrhea > grade 2.
• Has experienced thrombotic or embolic events within 6 months before the start of study treatment.
• Use of strong CYP3A4/CYP2C19 inducers (including rifampin and its analogues, and St. John's Wort) or strong CYP3A4/CYP2C19 inhibitors and/or strong UGT1A inhibitors within 14 days prior to signing the informed consent form.
• Has uncontrolled infection at screening.
• Patients with congenital or acquired immunodeficiency.
• Has a history of brain metastases or has brain metastases.
• Women who are pregnant or plan to become pregnant during the study treatment period.
• Other patients deemed unsuitable for inclusion by the treating physician.