Neoadjuvant Arterial Embolization Chemotherapy Combined PD-1 Inhibitor for Locally Advanced Rectal Cancer (NECI Study): a protocol for a phase II study

INTRODUCTION: The NICHE trial showed remarkable results of neoadjuvant immunotherapy in colorectal cancer patients with mismatch repair (MMR) deficiency (dMMR). However, rectal cancer patients with dMMR accounted for only 10% of case. The therapeutic effect is unsatisfactory in MMR-proficient patients. Oxaliplatin has been demonstrated to induce immunogenic cell death (ICD), which may improve the therapeutic effect of programmed cell death 1 blockade; however, a maximum tolerated dose is required to induce ICD. Arterial embolisation chemotherapy provides drugs locally and can easily reach the maximum tolerated dose, which could be a significant method for delivering chemotherapeutic agents. Therefore, we designed a multicenter, prospective, single-arm, phase II study. METHODS AND ANALYSIS: First, recruited patients will receive neoadjuvant arterial embolisation chemotherapy (NAEC) with oxaliplatin 85 mg/m(2) and 3 mg/m(2). After 2 days, three cycles of immunotherapy with intravenous tislelizumab (200 mg/body, day 1) will be initiated at an interval of 3 weeks. From the second cycle of immunotherapy, the XELOX regimen will be added. 3 weeks after neoadjuvant therapy finished, the operation will be initiated. Neoadjuvant Arterial Embolization Chemotherapy Combined PD-1 Inhibitor for Locally Advanced Rectal Cancer (NECI) Study combined arterial embolisation chemotherapy, immunotherapy and systemic chemotherapy. Based on this combination therapy, the maximum tolerated dose could easily be reached, and ICD could be induced by oxaliplatin easily. To our knowledge, the NECI Study is the first multicenter, prospective, single-arm, phase II clinical trial to assess the efficacy and safety of NAEC combined with tislelizumab and systemic chemotherapy in locally advanced rectal cancer. This study is expected to provide a new neoadjuvant therapeutic regimen for locally advanced rectal cancer. ETHICS AND DISSEMINATION: The Human Research Ethics Committee of the Fourth Affiliated Hospital of Zhejiang University School of Medicine approved this study protocol. The results will be published in peer-reviewed journals and presented at appropriate conferences. TRIAL REGISTRATION NUMBER: NCT05420584.