Neoadjuvant hepatic arterial infusion chemotherapy (HAIC) with GEMOX and lenvatinib in combination with adebrelimab for resectable high-risk recurrent intrahepatic cholangiocarcinoma (ICC): study protocol of the NEO-ERA-01 feasibility trial.

INTRODUCTION: Intrahepatic cholangiocarcinoma (ICC) has a high recurrence rate after curative surgery, with no standard neoadjuvant therapy. Hepatic arterial infusion chemotherapy (HAIC) has shown efficacy in locally advanced ICC, while immune checkpoint inhibitors and anti-angiogenic agents have demonstrated promising response rates. The NEO-ERA-01 study evaluates the feasibility of neoadjuvant HAIC-GEMOX plus lenvatinib and Adebrelimab in high-risk resectable ICC.

METHODS AND ANALYSIS: NEO-ERA-01 is a prospective, multicentre, phase II trial using Simon's two-stage design. Thirty patients with histologically confirmed resectable ICC and high-risk recurrence factors will be enrolled in China. Neoadjuvant therapy consists of HAIC-GEMOX (gemcitabine 800 mg/m², oxaliplatin 85 mg/m² every 3 weeks), lenvatinib (8 mg/day from Day 5) and Adebrelimab (1200 mg on Day 3, every 3 weeks) for 2-4 cycles. Surgery eligibility will be assessed post-treatment. Resected patients will receive adjuvant capecitabine (1250 mg/m² two times per day on Days 1-14, every 3 weeks) and Adebrelimab (1200 mg on Day 1, every 3 weeks) for 6 months.The primary endpoint is the completion rate of study treatment. Secondary endpoints include safety, R0 resection rate, response rate, event-free survival, disease-free survival and overall survival. Exploratory endpoints include immune microenvironment and biomarker analysis.

ETHICS AND DISSEMINATION: The study is approved by the ethics committee of all sites and follows the Declaration of Helsinki and good clinical practice guidelines. Results will be disseminated via peer-reviewed publications and conferences.

TRIAL REGISTRATION NUMBER: NCT06208462.