Pomej Katharina, Frick Adrian, Scheiner Bernhard, Balcar Lorenz, Pajancic Larissa, Klotz Anton, Kreuter Abelina, Lampichler Katharina, Regnat Katharina, Zinober Kerstin, Trauner Michael, Tamandl Dietmar, Gasche Christoph, Pinter Matthias
Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
Division of Gastroenterology and Hepatology, Department of Medicine III, Vienna Liver Cancer Study Group, Medical University of Vienna, Vienna, Austria.
PLoS One. 2025 Apr 15;20(4):e0321189. doi: 10.1371/journal.pone.0321189. eCollection 2025.
The gut microbiota is often altered in chronic liver diseases and hepatocellular carcinoma (HCC), and increasing evidence suggests that it may influence response to cancer immunotherapy. Strategies to modulate the gut microbiome (i.e., fecal microbiota transplant (FMT)) may help to improve efficacy of immune checkpoint inhibitors (ICIs) or even overcome resistance to ICIs. Here, we describe the design and rationale of FAB-HCC, a single-center, single-arm, phase II pilot study to assess safety, feasibility, and efficacy of FMT from patients with HCC who responded to PD-(L)1-based immunotherapy or from healthy donors to patients with HCC who failed to achieve or maintain a response to atezolizumab plus bevacizumab.
In this single-center, single-arm, phase II pilot study (ClinicalTrials.gov identifier: NCT05750030), we plan to include 12 patients with advanced HCC who failed to achieve or maintain a response to atezolizumab/bevacizumab. Patients will receive a single FMT via colonoscopy from donors with HCC who responded to PD-(L)1-based immunotherapy or from healthy individuals, followed by atezolizumab/bevacizumab every 3 weeks. The primary endpoint is safety, measured by incidence and severity of treatment-related adverse events. The main secondary endpoint is efficacy, as assessed by best radiological response according to RECISTv1.1 and mRECIST. Additional exploratory endpoints include data on the effect of FMT on recipient gut microbiota, as well as metagenomic analysis of stool samples, analyses of circulating immune cells and serum and stool proteomic, metabolomic and lipidomic signatures.
The results of this study will help to define the potential of FMT as add-on intervention in the systemic treatment of advanced HCC, with the potential to improve efficacy of immunotherapy or even overcome resistance.
EudraCT Number: 2022-000234-42 Clinical trial registry & ID: ClinicalTrials.gov identifier: NCT05750030 (Registration date: 16.01.2023).
肠道微生物群在慢性肝病和肝细胞癌（HCC）中常发生改变，越来越多的证据表明其可能影响癌症免疫治疗的反应。调节肠道微生物组的策略（即粪便微生物群移植（FMT））可能有助于提高免疫检查点抑制剂（ICI）的疗效，甚至克服对ICI的耐药性。在此，我们描述了FAB-HCC的设计和原理，这是一项单中心、单臂、II期试点研究，旨在评估从对基于PD-（L）1的免疫治疗有反应的HCC患者或健康供体向未实现或维持对阿替利珠单抗加贝伐单抗反应的HCC患者进行FMT的安全性、可行性和疗效。
在这项单中心、单臂、II期试点研究（ClinicalTrials.gov标识符：NCT05750030）中，我们计划纳入12例对阿替利珠单抗/贝伐单抗未实现或维持反应的晚期HCC患者。患者将通过结肠镜检查接受来自对基于PD-（L）1的免疫治疗有反应的HCC供体或健康个体的单次FMT，随后每3周接受一次阿替利珠单抗/贝伐单抗治疗。主要终点是安全性，通过治疗相关不良事件的发生率和严重程度来衡量。主要次要终点是疗效，根据RECISTv1.1和mRECIST通过最佳放射学反应进行评估。其他探索性终点包括FMT对受体肠道微生物群影响的数据，以及粪便样本的宏基因组分析、循环免疫细胞分析以及血清和粪便蛋白质组学、代谢组学和脂质组学特征分析。
本研究结果将有助于确定FMT作为晚期HCC全身治疗附加干预措施的潜力，有可能提高免疫治疗的疗效，甚至克服耐药性。
欧洲临床试验数据库编号：2022-000234-42 临床试验注册库及编号：ClinicalTrials.gov标识符：NCT05750030（注册日期：2023年1月16日）
