This is a randomized, noncomparative, open-label, exploratory clinical study designed to evaluate the efficacy and safety of sintilimab in combination with NALIRIFOX or gemcitabine plus cisplatin (GP) as first-line treatment for patients with metastatic biliary tract cancer (BTC) who have not received prior systemic anticancer therapy for metastatic disease.
Approximately 54 eligible participants will be randomized in a 1:1 ratio to two treatment groups. Participants in Group A will receive sintilimab in combination with NALIRIFOX, consisting of liposomal irinotecan (II), 5-fluorouracil/leucovorin, and oxaliplatin. Participants in Group B will receive sintilimab in combination with gemcitabine and cisplatin.
The primary endpoint is objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary endpoints include disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.
Aged 18 to 75 years, inclusive, at the time of signing the informed consent form, regardless of sex.
Histologically and/or cytologically confirmed biliary tract cancer, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer.
Presence of distant metastasis at the current disease stage.
No prior anticancer treatment for biliary tract cancer at the current disease stage, including radiotherapy, chemotherapy, immunotherapy, or biologic therapy.
History of a malignancy other than biliary tract cancer within 5 years before screening, except for adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or other malignancies considered by the investigator to have a low risk of metastasis and death.
Known central nervous system (CNS) metastases. Participants with suspected CNS metastases must undergo contrast-enhanced CT or MRI within 28 days before initiation of study treatment to exclude CNS metastases.
Prior treatment with an immune checkpoint inhibitor, including anti-PD-1, anti-PD-L1, anti-CTLA-4 therapy, or any cellular immunotherapy.
Prior irinotecan- or liposomal irinotecan-based chemotherapy.
Parallel
Sintilimab
DrugSintilimab 200 mg is administered by intravenous infusion on Day 1 every 3 weeks (Q3W) during combination treatment. Sintilimab is continued during maintenance treatment in participants without disease progression, according to the assigned treatment arm.
Irinotecan Hydrochloride Liposome Injection (II)
DrugIrinotecan hydrochloride liposome injection (II) 50 mg/m² is administered by intravenous infusion over 90 minutes (±30 minutes), or according to institutional clinical practice, on Day 1 every 2 weeks (Q2W). It is administered as part of the NALIRIFOX regimen and is continued during maintenance treatment in eligible participants without disease progression.
Oxaliplatin
DrugOxaliplatin 60 mg/m² is administered by intravenous infusion over 2 hours, or according to institutional clinical practice, on Day 1 every 2 weeks (Q2W) as part of the NALIRIFOX combination treatment. Oxaliplatin is not included in the maintenance regimen.
Leucovorin
DrugLeucovorin 200 mg/m² is administered by intravenous infusion over 1 hour, or according to institutional clinical practice, on Day 1 every 2 weeks (Q2W) as part of the NALIRIFOX regimen. Leucovorin is continued during maintenance treatment in eligible participants without disease progression.
Fluorouracil
DrugFluorouracil 2000 mg/m² is administered as a continuous intravenous infusion over 46 to 48 hours, or according to institutional clinical practice, starting on Day 1 every 2 weeks (Q2W) as part of the NALIRIFOX regimen. Fluorouracil is continued during maintenance treatment in eligible participants without disease progression.
gemcitabine
DrugGemcitabine 1000 mg/m² is administered by intravenous infusion over 30 minutes on Days 1 and 8 of each 3-week cycle (Q3W). It is administered with cisplatin and sintilimab during combination treatment and is continued with sintilimab during maintenance treatment in eligible participants without disease progression.
Cisplatin
DrugCisplatin 25 mg/m² is administered by intravenous infusion on Days 1 and 8 of each 3-week cycle (Q3W) as part of the gemcitabine, cisplatin, and sintilimab combination regimen. Cisplatin is not included in the maintenance regimen.
Objective Response Rate (ORR)
ORR is defined as the proportion of participants who achieve a best overall response of complete response (CR) or partial response (PR), as assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Disease Control Rate (DCR)
DCR is defined as the proportion of participants who achieve CR, PR, or stable disease (SD) according to RECIST version 1.1.
Progression-Free Survival (PFS)
PFS is defined as the time from enrollment and initiation of study treatment to the first documented radiographic disease progression according to RECIST version 1.1 or death from any cause, whichever occurs first.
Overall Survival (OS)
OS is defined as the time from enrollment and initiation of study treatment to death from any cause. Participants who are alive at the end of the study will be censored at the last date they are known to be alive.
Number and Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
The number and percentage of participants experiencing treatment-emergent adverse events (TEAEs) will be summarized. Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.
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