Disitamab Vedotin Plus Lenvatinib and PD-1 Inhibitors for Treating HER2-positive Advanced Biliary Tract Cancer

Inclusion criteria

• Participants who voluntarily participate in this study, sign the written informed consent, and are able to comply with the protocol.
• Age ≥ 18 years and any gender.
• Histologically or cytologically confirmed unresectable locally advanced or metastatic biliary tract cancer (BTC), including intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), and gallbladder cancer (GBC).
• At least one measurable lesion (according to RECIST 1.1).
• ECOG performance status score of 0-1.
• Child-Pugh score ≤ 7 .
• HER2 expression confirmed by: Immunohistochemistry (IHC 2+ or 3+); or Fluorescence in situ hybridization (FISH) with HER2/CEP17 ratio ≥2.0; or Next-generation sequencing (NGS) showing HER2 amplification.
• No prior HER2-targeted therapy (including antibody-based agents, small-molecule TKIs, or antibody-drug conjugates) before randomization.
• Expected survival > 12 weeks.
• Adequate hematological and major organ function.

Exclusion criteria

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• Histological or cytological diagnosis of combined hepatocellular-cholangiocarcinoma (cHCC-CCA), mucinous adenocarcinoma, sarcoma, or neuroendocrine tumors.
• Pregnant women (positive pregnancy test before medication) or lactating women.
• Known allergy or intolerance to disitamab vedotin, lenvatinib, PD-1 inhibitors, or their excipients.
• History of other active malignancies within 5 years prior to screening.
• Presence of central nervous system metastasis and/or leptomeningeal metastasis.
• Unhealed severe wounds, active ulcers, or untreated fractures.
• Administration of live vaccines within 30 days prior to randomization.
• Active autoimmune disease or history of autoimmune disease.
• Presence of clinically significant gastrointestinal disorders.
• Presence of clinically significant cardiovascular or cerebrovascular diseases.