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

A Prospective Exploratory Phase II Study of Disitamab Vedotin Plus Lenvatinib and PD-1 Inhibitors for the Treatment of HER2-positive Advanced Biliary Tract Cancer

This trial is a single-arm exploratory phase II clinical study initiated by the investigator.

Subjects who met the research criteria were screened and enrolled to receive the treatment regimen of disitamab vedotin combined with lenvatinib and PD-1 inhibitor. During the treatment process, the researchers closely followed up, strictly evaluated the efficacy, assessed the efficacy and safety of the subjects after receiving the combined treatment, evaluated the subjects until progression occurred, and observed their objective response rate, progression-free survival, overall survival, disease control rate, duration of response, and safety evaluation.

Inclusion criteria:

1. Participants who voluntarily participate in this study, sign the written informed consent, and are able to comply with the protocol.
2. Age ≥ 18 years and any gender.
3. Histologically or cytologically confirmed unresectable locally advanced or metastatic biliary tract cancer (BTC), including intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), and gallbladder cancer (GBC).
4. At least one measurable lesion (according to RECIST 1.1).
5. ECOG performance status score of 0-1.
6. Child-Pugh score ≤ 7 .
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.
8. No prior HER2-targeted therapy (including antibody-based agents, small-molecule TKIs, or antibody-drug conjugates) before randomization.
9. Expected survival > 12 weeks.
10. Adequate hematological and major organ function.

Exclusion criteria：

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