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).
Parallel
Trastuzumab Rezetecan
DrugThe recommended dosage is 4.8 mg/kg. A fixed dose of 408 mg is administered for patients weighing ≥85 kg. It is given via intravenous infusion every 3 weeks (Q3W). The first infusion should be administered over 90 minutes. If the prior infusion was well-tolerated, subsequent infusions may be shortened to 30 minutes.
Adebrelimab
DrugA fixed dose of 1200 mg is administered via intravenous infusion every 3 weeks (±3 days). The infusion duration should be controlled between 30 and 60 minutes and must not exceed 2 hours.
Lenvatinib
DrugAdministered orally once daily with food (preferably at the same time each day). The dose is 12 mg/day for patients weighing ≥60 kg and 8 mg/day for those \<60 kg. The dose can be de-escalated based on toxicity according to the following scheme: 12 mg/day → 8 mg/day → 4 mg/day → discontinuation. If the investigator deems the patient intolerant, dose reduction across levels may be considered if deemed necessary.
Objective response rate
Using imaging for assessment
Overall Survival
Overall Survival (OS) was defined as the time from randomization (or treatment initiation) to death from any cause.
duration of response
DoR was measured from the date of the first documented objective tumor response (per RECIST 1.1 criteria) to the date of the first documented progression or death from any cause.
disease control rate
DCR was assessed per RECIST 1.1 and refers to the proportion of patients whose tumor shrinkage or control met the predefined criteria and was maintained for a minimum specified duration, encompassing CR, PR, and SD.
progression-free survival
Progression-Free Survival (PFS) was defined as the time from treatment initiation to the first occurrence of disease progression or death from any cause.
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