Advanced biliary tract cancer has a poor prognosis and limited efficacy with current regimens. This multicenter single-arm phase Ib/II trial explores the efficacy and safety of HAI-GP chemotherapy combined with intraoperative arterial envafolimab and lenvatinib as first-line therapy for unresectable BTC. It conducts dose exploration to confirm the optimal dosage and evaluates clinical outcomes, aiming to establish a better comprehensive treatment strategy.
Age between 18 years and [missing value] years, inclusive.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Histologically or cytologically confirmed biliary tract carcinoma, deemed unsuitable for radical surgical resection.
At least one measurable lesion as determined by the investigator in accordance with mRECIST or RECIST version 1.1.
Known hypersensitivity to the investigational drug(s).
Current participation in another interventional clinical trial, or receipt of any investigational drug or use of investigational device within 4 weeks prior to first dosing.
History of malignancy outside the biliary tract within 5 years prior to first dosing, except for adequately treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or carcinoma in situ that has been completely resected.
Previous treatment with immune checkpoint inhibitors including anti-PD-1, anti-PD-L1, or anti-PD-L2 agents, or drugs targeting other stimulatory or co-inhibitory T-cell receptors (e.g., CTLA-4, OX-40, CD137).
Single group
HAIC Combined Regimen Treatment Group
DrugIn Phase Ib, nine patients will be enrolled and allocated to three dose cohorts to receive the combination regimen of HAIC (GP) + intra-arterial infusion of envafolimab + lenvatinib. Dose-limiting toxicities (DLTs) will be monitored for 28 days following administration. If no DLTs occur, the regimen will be considered tolerable, and patients will continue follow-up until 60 days post-administration. Investigators confirm Phase II initiation and optimal dose per safety data. In Phase II, 20 subjects adopt the optimized dose regimen. They firstly receive two cycles of combined treatment for efficacy evaluation. Those with clinical benefits finish six cycles in total, then switch to maintenance treatment until treatment ends, disease progresses, adverse reactions are intolerable, subjects withdraw consent or treatment is terminated by researchers. Robotic arm is applied to assist accurate hepatic artery catheterization and stable drug infusion during interventional procedures.
Primary endpoint for Phase Ib: Dose-Limiting Toxicity (DLT)
The DLT observation period extends from the first dose to 28 days post-administration. If, among 9 patients enrolled in Phase Ib, the number experiencing DLT is ≤1 ，the dose level will be considered well tolerated; if the number is ≥2, dose reduction and re-evaluation will be required until a well-tolerated dose is established as the Recommended Phase II Dose (RP2D).
Primary endpoint for Phase II:Objective Response Rate (ORR)
Primary endpoint for Phase II:Objective Response Rate (ORR), defined as the proportion of patients achieving a predefined reduction in tumor volume maintained for the minimum required duration, including Complete Response (CR) and Partial Response (PR).
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