Clinical and biomarker analyses of SHR-1701 combined with famitinib in patients with previously treated advanced biliary tract cancer or pancreatic ductal adenocarcinoma:a phase II trial  

作　　者：Lixia Yi Haoqi Pan Zhouyu Ning Litao Xu Hena Zhang Longfei Peng Yaowu Liu Yifan Yang Waimei Si Ying Wang Xiaoyan Zhu Shenglin Huang Zhiqiang Meng Jing Xie 

机构地区：[1]Department of Integrative Oncology,Fudan University Shanghai Cancer Center,Shanghai,China [2]Department of Minimally Invasive Therapy Center,Fudan University Shanghai Cancer Center,Shanghai,China [3]Department of Oncology,Shanghai Medical College,Fudan University,Shanghai,China [4]Shanghai Key Laboratory of Medical Epigenetics,Institutes of Biomedical Sciences,Fudan University,Shanghai,China [5]Suzhou Institute of Biomedical Engineering and Technology,Chinese Academy of Sciences,Suzhou,China [6]Clinical Research&Development,Jiangsu Hengrui Pharmaceuticals Co.,Ltd.,Shanghai,China

出　　处：《Signal Transduction and Targeted Therapy》2025年第1期328-339,共12页信号转导与靶向治疗(英文)

摘　　要：Advanced biliary tract cancer(BTC)and pancreatic ductal adenocarcinoma(PDAC)have poor prognoses and limited treatment options.Here,we conducted thisfirst-in-class phase II study to evaluate the efficacy and safety of SHR-1701,a bifunctional fusion protein targeting programmed death-ligand 1(PD-L1)and transforming growth factor-beta(TGF-β),combined with famitinib,a multi-targeted receptor tyrosine kinase inhibitor,in patients with advanced BTC or PDAC who failed previous standard treatment(trial registration:ChiCTR2000037927).Among 51 enrolled patients,the BTC cohort showed an objective response rate(ORR)of 28%(including 2 complete responses)and a disease control rate(DCR)of 80%,with a median progression-free survival(mPFS)of 5.1 months and a median overall survival(mOS)of 16.0 months.In the PDAC cohort,the ORR was 15%(2 complete responses),with a DCR of 60%,and the mPFS and mOS were 2.1 months and 5.3 months,respectively.Grade 3 or 4 treatment-related adverse events(TRAEs)occurred in 29.4%of patients,with no grade 5 TRAEs reported.Exploratory analyses revealed that primary tumor resection history,peripheral blood immunophenotype changes,and distinct immune-metabolic profiles were associated with treatment benefits.An immune/metabolism score integrating the features of six genes was developed as a predictive biomarker for immunotherapy response in multiple cohorts,allowing for the selection of patients most likely to experience positive outcomes from this therapy regimen.In conclusion,our study provides proof-of-concept data supporting the potential of SHR-1701 plus famitinib as an effective and safe subsequent-line therapy for refractory BTC and PDAC,highlighting the promise of targeting PDL1,TGF-β,and angiogenesis pathways simultaneously.

关 键 词：PATIENTS ADENOCARCINOMA METABOLISM 

分 类 号：R73[医药卫生—肿瘤]