Adebrelimab Plus S-1 for Resected Cholangiocarcinoma

A Single-Arm, Exploratory Clinical Study of Adebrelimab Combined With S-1 in Patients With Resected Cholangiocarcinoma

The goal of this clinical trial is to learn whether adebrelimab combined with S-1 works as an adjuvant treatment for patients with cholangiocarcinoma after curative surgery. It will also learn about the safety of this treatment. The main questions it aims to answer are:

• Does adebrelimab combined with S-1 reduce the risk of cancer recurrence after surgery?
• What side effects do participants experience when receiving this treatment? All participants in this study will receive adebrelimab combined with S-1. There is no comparison group in this study.

Participants will:

• Receive adebrelimab by intravenous infusion once every 3 weeks for 4 cycles
• Take S-1 by mouth twice daily for 4 weeks, followed by a 2-week rest, for 4 cycles
• Visit the hospital regularly for checkups, laboratory tests, and imaging examinations (CT or MRI)
• Be followed up for safety and survival after completing treatment

Cholangiocarcinoma is a highly aggressive malignancy with poor prognosis. Although curative surgical resection remains the only potentially curative treatment, the majority of patients experience recurrence or metastasis after surgery. Therefore, effective adjuvant treatment strategies are urgently needed to improve survival outcomes.

S-1, an oral fluoropyrimidine-based chemotherapy, has demonstrated survival benefits as adjuvant therapy in biliary tract cancer. However, its efficacy remains limited, and further improvement is needed. Immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway have shown promising antitumor activity in various malignancies, including biliary tract cancer. Combining immunotherapy with chemotherapy may enhance antitumor immune responses and improve clinical outcomes.

This study is a single-arm, exploratory clinical trial designed to evaluate the efficacy and safety of adebrelimab in combination with S-1 as adjuvant therapy in patients with cholangiocarcinoma after curative resection.

Approximately 40 patients with histologically confirmed cholangiocarcinoma who have undergone curative surgical resection will be enrolled. Patients will initiate study treatment within 4 to 8 weeks after surgery. Adebrelimab will be administered at a dose of 1200 mg intravenously on Day 1 of each 3-week cycle for a total of 4 cycles. S-1 will be administered orally at 40 mg/m² twice daily on Days 1 to 28 of each 6-week cycle, followed by a 2-week rest period, for a total of 4 cycles.

Tumor assessments will be performed using CT or MRI according to RECIST version 1.1 at regular intervals. Safety will be evaluated based on adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.

The primary endpoint is the 1-year relapse-free survival (RFS) rate. Secondary endpoints include relapse-free survival (RFS), overall survival (OS), and safety.

Patients will be followed for safety for 90 days after the last dose and then for survival every 3 months until disease progression, death, loss to follow-up, or study termination.

This study aims to explore the potential benefit of combining immunotherapy with chemotherapy as postoperative adjuvant treatment and to provide preliminary evidence for improving outcomes in patients with cholangiocarcinoma.

Inclusion Criteria:

• Histologically or pathologically confirmed malignant cholangiocarcinoma.
• Patients who have undergone curative surgical resection.
• Age between 18 and 75 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Expected survival time >3 months.
• Adequate organ and bone marrow function, including:Absolute neutrophil count ≥1.5 × 10^9/L,Platelet count ≥75 × 10^9/L,Hemoglobin ≥90 g/L,Total bilirubin ≤1.5 × upper limit of normal (ULN),AST and ALT ≤2.5 × ULN,Albumin ≥3 g/dL,Serum creatinine ≤1.5 × ULN.
• Ability to understand and willingness to sign written informed consent.
• For patients of childbearing potential, willingness to use effective contraception during the study and for at least 1 month after the last dose; negative pregnancy test within 72 hours prior to enrollment.

Exclusion Criteria:

• Prior treatment with immune checkpoint inhibitors or other agents targeting T-cell co-stimulatory or co-inhibitory pathways (e.g., CTLA-4, CD137).
• Use of any investigational drug within 4 weeks prior to enrollment.
• Active autoimmune disease or history of autoimmune disease (e.g., interstitial lung disease, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, myocarditis, nephritis, hyperthyroidism, or hypothyroidism requiring hormone replacement).
• Known immunodeficiency, including HIV infection, active hepatitis B (HBV DNA >500 IU/mL), active hepatitis C (HCV RNA above detection limit), or co-infection of HBV and HCV.
• Severe infection within 4 weeks prior to first dose or unexplained fever >38.5°C during screening.
• History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
• Uncontrolled psychiatric disorders.
• Severe or uncontrolled comorbidities that may interfere with study participation (e.g., unstable angina, myocardial infarction within 6 months, symptomatic arrhythmia, congestive heart failure, uncontrolled diabetes, or uncontrolled infection).
• History of other malignancies within the past 5 years, except for non-melanoma skin cancer or carcinoma in situ.
• Known hypersensitivity to study drugs or monoclonal antibodies.
• Inability or unwillingness to provide informed consent.