NUC-1031/cisplatin versus gemcitabine/cisplatin in untreated locally advanced/metastatic biliary tract cancer (NuTide:121)

Gemcitabine/cisplatin is standard of care for first-line treatment of patients with advanced biliary tract cancer (aBTC); new treatments are needed. NUC-1031 is designed to overcome key cancer resistance mechanisms associated with gemcitabine. The tolerability/efficacy signal of NUC-1031/cisplatin in the Phase Ib ABC-08 study suggested that this combination may represent a more efficacious therapy than gemcitabine/cisplatin for patients with aBTC, leading to initiation of the global NuTide:121 study which will include 828 patients ≥18 years with untreated histologically/cytologically-confirmed aBTC (including cholangiocarcinoma, gallbladder or ampullary cancer); randomized (1:1) to NUC-1031 (725 mg/m2)/cisplatin (25 mg/m2) or gemcitabine (1000 mg/m2)/cisplatin (25 mg/m2), on days 1/8, Q21-days. Primary objectives are overall survival and objective response rate. Secondary objectives: progression-free survival, safety, pharmacokinetics, patient-reported quality of life and correlative studies. (Investigational new drug (IND) number: 139058, European Clinical Trials database: EudraCT Number 2019-001025-28, ClinicalTrials.gov identifier: NCT04163900). A PDF version of this infographic is available as supplemental material.吉西他滨联合顺铂是晚期胆道癌（advanced biliary tract cancer, aBTC）患者一线治疗的标准方案，目前仍亟需新型治疗手段。NUC-1031的设计初衷为克服与吉西他滨相关的关键肿瘤耐药机制。在Ib期ABC-08研究中，NUC-1031联合顺铂的耐受性与疗效信号提示，该联合方案或较吉西他滨/顺铂更具治疗优势，可用于aBTC患者，由此启动了全球NuTide:121研究。该研究共纳入828例年满18岁、未经治疗且经组织学或细胞学确认的aBTC患者（涵盖胆管癌、胆囊癌及壶腹癌），按1:1比例随机分配至NUC-1031（725 mg/m²）联合顺铂（25 mg/m²）组，或吉西他滨（1000 mg/m²）联合顺铂（25 mg/m²）组，给药方案为第1、8天给药，每21天为一个治疗周期。本研究的主要终点为总生存期与客观缓解率；次要终点包括无进展生存期、安全性、药代动力学、患者报告的生活质量以及相关研究。本研究的研究性新药（Investigational New Drug, IND）编号为139058，欧盟临床试验数据库（EudraCT）编号为2019-001025-28，ClinicalTrials.gov标识符为NCT04163900。本信息图的PDF版本可作为补充材料获取。