Addition of SHR-1701 to first-line capecitabine and oxaliplatin(XELOX) plus bevacizumab for unresectable metastatic colorectal cancer  

作　　者：Miao-Zhen Qiu Yuxian Bai Jufeng Wang Kangsheng Gu Mudan Yang Yifu He Cheng Yi Yongdong Jin Bo Liu Feng Wang Yu-kun Chen Wei Dai Yingyi Jiang Chuanpei Huang Rui-Hua Xu Hui-Yan Luo 

机构地区：[1]Department of Medical Oncology,Sun Yat-sen University Cancer Center,State Key Laboratory of Oncology in South China,Guangdong Provincial Clinical Research Center for Cancer,Sun Yat-sen University,Guangzhou,PR China [2]Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer,Chinese Academy of Medical Sciences,Guangzhou,PR China [3]Department of Gastroenterology 1,Harbin Medical University Cancer Hospital,Harbin,PR China [4]Department of Medical Oncology,The Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer Hospital,Zhengzhou,PR China [5]Oncology Ward 1,The First Affiliated Hospital of Anhui Medical University,Hefei,PR China [6]Gastroenterology Ward(2),Shanxi Provincial Cancer Hospital,Taiyuan,PR China [7]Medical Oncology Ward 1,Anhui Provincial Cancer Hospital,Hefei,PR China [8]Abdominal Oncology,West China Hospital of Sichuan University,Chengdu,PR China [9]Department of Medical Oncology,Sichuan Cancer Hospital&Institute,Sichuan Cancer Center,School of Medicine,University of Electronic Science&Technology of China,Chengdu,PR China [10]Gastroenterology Ward 3,Cancer Hospital Affiliated to Shandong First Medical University,Jinan,PR China [11]Oncology Department 1,The First Affiliated Hospital of Zhengzhou University,Zhengzhou,PR China [12]Clinical Research&Development,Jiangsu Hengrui Pharmaceuticals Co.,Ltd,Shanghai,PR China

出　　处：《Signal Transduction and Targeted Therapy》2025年第1期340-349,共10页信号转导与靶向治疗(英文)

基　　金：supported by Jiangsu Hengrui Pharmaceuticals and the following grants:the National Natural Science Foundation of China(NSFC:82321003,82173128,82073377,81930065);the Natural Science Foundation of Guangdong(2021A1515012439);Guangdong Basic and Applied Basic Research Foundation(2024B1515020120);the CAMS Innovation Fund for Medical Sciences(CIFMS:2019-I2M-5-036);Additional funding was provided by the Cancer Innovative Research Program of Sun Yat-sen University Cancer Center(CIRP-SYSUCC-0004).

摘　　要：This phase 2/3 trial (NCT04856787) assessed the efficacy and safety of SHR-1701, a bifunctional protein targeting PD-L1 and TGF-β,in combination with BP102 (a bevacizumab biosimilar) and XELOX (capecitabine plus oxaliplatin) as a first-line treatment forunresectable metastatic colorectal cancer (mCRC). In this phase 2 study, a total of 62 patients with untreated, histologicallyconfirmed colorectal adenocarcinoma and no prior systemic therapy for metastatic disease were enrolled. Patients receivedSHR-1701 (30 mg/kg), bevacizumab (7.5 mg/kg), and oxaliplatin (130 mg/m^(2)) intravenously on day 1, along with oral capecitabine(1 g/m^(2) twice daily) on days 1-14 of 21-day cycles. Up to eight induction cycles were administered, followed by maintenancetherapy for responders or those with stable disease. The primary endpoints were safety and objective response rate (ORR) perRECIST v1.1. The combination achieved an ORR of 59.7% and a disease control rate (DCR) of 83.9%. Median progression-free survival(PFS) was 10.3 months (95% CI: 8.3-13.7), with 6- and 12-month PFS rates of 77.2% and 41.3%, respectively. The estimated12-month overall survival (OS) rate was 67.7%. Grade ≥3 treatment-related adverse events (TRAEs) were reported in 59.7% ofpatients, with anemia and neutropenia (8.1% each) being the most common. Retrospective DNA sequencing revealed that hightumor mutational burden, neo-antigens, and SBS15 enrichment correlated with better responses. Elevated baseline lactatedehydrogenase was linked to shorter PFS. SHR-1701 combined with XELOX and bevacizumab demonstrated a manageable safetyprofile and potent antitumor activity in unresectable mCRC.

关 键 词：BEVACIZUMAB colorectal SHR 

分 类 号：R73[医药卫生—肿瘤]