A phase II clinical trial of toripalimab in advanced solid tumors with polymerase epsilon/polymerase delta(POLE/POLD1)mutation  

作　　者：Ying Jin Run-Jie Huang Wen-Long Guan Zhi-Qiang Wang Zong-Jiong Mai Yu-Hong Li Jian Xiao Xing Zhang Qi Zhao Shi-Fu Chen Ming Liu Yan-Xia Shi Feng Wang Rui-Hua Xu 

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,510060,People’s Republic of China [2]Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer,Chinese Academy of Medical Sciences,Guangzhou,510060,People’s Republic of China [3]Department of Oncology,The Fifth Affiliated Hospital of Sun Yat-sen University,Zhuhai,519000,People’s Republic of China [4]Department of Medical Oncology,Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences),Southern Medical University,Guangzhou,510100,People’s Republic of China [5]Department of Medical Melanoma and Sarcoma,Sun Yat-sen University Cancer Center,State Key Laboratory of Oncology in South China,Collaborative Innovation Center for Cancer Medicine,Sun Yat-sen University,Guangzhou,510060,People’s Republic of China [6]Bioinformatic Platform,Sun Yat-sen University Cancer Center,State Key Laboratory of Oncology in South China,Collaborative Innovation Center for Cancer Medicine,Sun Yat-sen University,Guangzhou,510060,People’s Republic of China [7]HaploX Biotechnology,Shenzhen,518000,People’s Republic of China

出　　处：《Signal Transduction and Targeted Therapy》2024年第10期4543-4553,共11页信号转导与靶向治疗（英文）

基　　金：National Natural Science Foundation of China(82321003,81930065,82173128);CAMS Innovation Fund for Medical Sciences(CIFMS)(2019-I2M-5-036);Science and Technology Program of Guangzhou(202206080011);Medical Scientific Research Foundation of Guangdong Province(A2022054);Cancer Innovative Research Program of Sun Yat-sen University Cancer Center(CIRP-SYSUCC-0004);Sun Yat-sen University Clinical Research 5010 Program(84000-31630002);Fundamental Research Funds for the Central Universities,Sun Yat-sen University(22yklj06);Young Talents Program of Sun Yat-sen University Cancer Center(YTP-SYSUCC-0018);CSCO foundation(Y-QL202202-0089).

摘　　要：Patients carrying mutations in polymerase epsilon/polymerase delta have shown positive responses to immune checkpoint inhibitors.Yet,prospective trials exploring the efficacy in those with polymerase epsilon/polymerase delta mutations are still lacking.A phase II clinical trial was initiated to evaluate the efficacy of toripalimab,a humanized IgG4K monoclonal antibody to human PD-1,in patients with advanced solid tumors with unselected polymerase epsilon/polymerase delta mutations but without microsatellite instability-high.A total of 15 patients were enrolled,14 of whom were assessed for treatment efficacy.There was a 21.4%overall response rate,with a disease control rate of 57.1%.The median overall survival and median progression-free survival were 17.9(95%CI 13.5-not reach)months and 2.5(95%CI 1.4-not reach)months,respectively.For patients with exonuclease domain mutations,the objective response rate was 66.7%(2/3),with a disease control rate of 66.7%(2/3).For those with non-exonuclease domain mutations,the rates were 9.1%(1/11)and 54.5%(6/11),respectively.Notably,patients with PBRM1 gene mutations exhibited a high response rate to toripalimab at 75.0%(3/4).This study showed that neither the exonuclease domain mutations nor non-exonuclease domain mutations could fully predict the efficacy of immunotherapy,urging the need for more investigations to clarify potential immune sensitization differences within polymerase epsilon/polymerase delta mutation variants.

关 键 词：DELTA phase NEITHER 

分 类 号：R730[医药卫生—肿瘤]