This is a prospective, single-arm, exploratory interventional study designed to evaluate the efficacy and safety of liposomal irinotecan (II) plus fluorouracil/leucovorin (5-FU/LV) and sintilimab with sequential stereotactic body radiation therapy (SBRT) as first-line treatment for patients with unresectable locally advanced biliary tract cancer (BTC) who have not received prior systemic anticancer therapy for their current disease.
Approximately 31 participants will be enrolled. Participants will receive liposomal irinotecan (II), 5-FU/LV, and sintilimab. Participants without disease progression after initial systemic treatment will receive sequential SBRT to the primary biliary tract tumor. After eight administrations of chemotherapy (approximately 16 weeks), resectability will be assessed by a multidisciplinary team. Participants considered eligible for surgery will undergo radical surgical resection followed by adjuvant treatment, whereas those who remain unresectable will continue the study treatment until disease progression or another protocol-defined reason for discontinuation.
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), surgical conversion rate (SCR), and safety.
Aged 18 to 80 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.
Unresectable locally advanced disease at the current disease stage, as determined by a multidisciplinary team (MDT).
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 cured basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or other malignancies considered by the investigator and multidisciplinary team 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.
Single group
Irinotecan Hydrochloride Liposome Injection (II)
DrugLiposomal irinotecan (II) 60 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).
Fluorouracil
DrugFluorouracil (5-FU) 2000 mg/m² is administered as a continuous intravenous infusion over 46 hours on Day 1 every 2 weeks (Q2W).
Leucovorin
DrugLeucovorin (LV) 200 mg/m² is administered by intravenous infusion over more than 30 minutes on Day 1 every 2 weeks (Q2W).
Sintilimab
DrugSintilimab 200 mg is administered by intravenous infusion on Day 1 every 3 weeks (Q3W).
Stereotactic Body Radiation Therapy
RadiationParticipants without disease progression after four administrations of chemotherapy will receive stereotactic body radiation therapy (SBRT) to the primary biliary tract tumor between the sixth and seventh chemotherapy administrations. The prescribed radiation doses are 50 Gy in 10 fractions to the planning gross tumor volume (PGTV) and 30 Gy in 10 fractions to the planning target volume (PTV).
Radical Surgical Resection
Procedure/SurgeryAfter eight administrations of chemotherapy (approximately 16 weeks), participants will undergo multidisciplinary evaluation for surgical resectability. Participants considered surgically resectable will undergo radical surgical resection. Successful conversion is defined as R0 or R1 resection.
Objective Response Rate (ORR)
ORR is defined as the proportion of participants with 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 with a best overall response of complete response (CR), partial response (PR), or stable disease (SD), as assessed 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.
Surgical Conversion Rate (SCR)
SCR is defined as the proportion of treated participants who successfully undergo surgical conversion. Successful conversion is defined as R0 or R1 surgical resection following conversion therapy.
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