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 .