Adebrelimab combined with anlotinib plus hepatic arterial infusion chemotherapy or intravenous chemotherapy for first-line treatment of advanced biliary tract cancer: protocol for a randomized open-label clinical study.

BACKGROUND: Malignancies of the biliary tract system, commonly termed biliary tract carcinoma (BTC), and primarily include cholangiocarcinoma (CC). BTC is most often diagnosed at an advanced stage, when surgical resection is no longer feasible, and systemic therapy is therefore frequently used. Immunotherapy, antiangiogenic targeted treatments, precision medicine, and chemotherapy have all improved the management of BTC in recent years. While arterial infusion chemotherapy has demonstrated notable efficacy in hepatocellular carcinoma, its role and outcomes in CC remain less defined, with limited and sometimes inconsistent study results, necessitating further investigation. However, these strategies continue to fall short of meeting full clinical needs, and limitations remain prominent.

METHODS: This randomized, open-label, multicenter phase II trial will enroll 60 participants with advanced BTC. The inclusion criteria comprised: age >18 years, advanced BTC diagnosis, no prior systemic therapy, at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Eastern Cooperative Oncology Group (ECOG) performance status 0-1.Participants are randomized 1:1 to Cohort 1 [one cycle of hepatic arterial infusion gemcitabine + oxaliplatin (GEMOX) followed by one cycle of intravenous GEMOX] or Cohort 2 (two cycles of intravenous GEMOX). Both cohorts receive intravenous adebrelimab (1,200 mg, day 1) and oral anlotinib (12 mg daily, 2 weeks on/1 week off) per 21-day cycle. After combination chemotherapy, patients with clinical benefit continue adebrelimab plus anlotinib. We will conduct safety visits on the first day of each cycle. The primary endpoint is the 6-month progression-free survival (PFS) rate. Secondary endpoints include PFS, objective response rate, overall survival, and safety.

DISCUSSION: This trial aims to demonstrate the efficacy and safety of adebrelimab combined with anlotinib and GEMOX in advanced BTC, with an expectation that arterial infusion chemotherapy may improve 6-month PFS. We expect that arterial infusion chemotherapy may have better 6-month PFS rate.

TRIAL REGISTRATION: This clinical trial has been registered on the Chinese Clinical Trial Registry. Clinical trial information: ChiCTR2500102333.