This phase II study evaluates the efficacy and safety of Trastuzumab Rezetecan in combination with Adebrelimab and Lenvatinib as first-line therapy for patients with locally advanced or metastatic HER2-positive or HER2-low biliary tract cancer. The primary objective is the objective response rate (ORR). Key secondary objectives include efficacy endpoints-progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and duration of response (DoR)-and safety assessments comprising adverse events (AEs), serious adverse events (SAEs), vital signs, and laboratory findings.
The HER2-positive subjects voluntarily participated in the study and agreed to sign the written informed consent form, and they had good compliance.
Age ≥ 18 years old, gender not limited;
Locally advanced or metastatic cholangiocarcinoma, including cholangiocarcinoma (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma) and gallbladder cancer, which has been confirmed by pathological histology or cytology;
Not suitable for radical surgical resection or local treatment. Subjects who have not received any systemic anti-tumor therapy in the past; allowed to have received radical treatment previously (including surgical treatment and postoperative adjuvant chemotherapy and/or radiotherapy), and the interval from the last administration of radical treatment to disease recurrence is at least 6 months, and no systemic anti-tumor treatment was received during the recurrence or metastasis stage.
Histological or cytological pathology confirmed that the bile duct tumors were of non-adenocarcinoma pathological types such as ampullary carcinoma, small cell carcinoma, neuroendocrine tumor, sarcoma, mucinous cystic tumor, etc.
Having another active malignant tumor within 5 years or simultaneously; excluding cervical carcinoma in situ that has been fully treated, as well as basal cell or squamous cell carcinomas of the skin.
Participants who have previously received immunotherapy, HER2-targeted, or ADC drug treatment, including immune checkpoint inhibitors (such as anti-PD-1/L1 antibodies, anti-CTLA-4 antibodies, anti-TIGIT antibodies, anti-LAG3 antibodies, etc.), immune checkpoint agonists (such as CD40, CD137, OX40 antibodies, etc.), and any other treatments targeting the immune mechanism of tumor treatment;
The adverse reactions from previous anti-tumor treatments have not yet recovered to a NCI-CTCAE v5.0 rating of ≤ 1 (excluding cases of hair loss, meeting the numerical requirements of the inclusion criteria, or other situations determined by the investigator not to affect the treatment with the study drug).