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

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外文摘要：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 lgG4K 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％Cl 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.

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

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作者单位：

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

Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer,Chinese Academy of Medical Sciences,Guangzhou 510060,People's Republic of China

Department of Oncology,The Fifth Affiliated Hospital of Sun Yat-sen University,Zhuhai 519000,People's Republic of China

Department of Medical Oncology,Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences),Southern Medical University,Guangzhou 510100,People's Republic of China

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

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

HaploX Biotechnology,Shenzhen 518000,People's Republic of China

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基金：

tNational Natural Science Foundation of ChinatNational Natural Science Foundation of ChinatNational Natural Science Foundation of ChinaCAMS Innovation Fund for Medical Sciences(CIFMS)Science and Technology Program of GuangzhouMedical Scientific Research Foundation of Guangdong ProvinceCancer Innovative Research Program of Sun Yatsen University Cancer CenterSun Yatsen University Clinical Research 5010 ProgramFundamental Research Funds for the Central Universities,Sun Yatsen UniversityYoung Talents Program of Sun Yatsen University Cancer CenterCSCO foundation

项目编号：

8232100381930065821731282019-I2M-5-036202206080011A2022054CIRP-SYSUCC-000484000-3163000222yklj06YTP-SYSUCC-0018Y-QL202202-0089

出版年：

2024

DOI：

10.1038/s41392-024-01939-5

信号转导与靶向治疗(英文)

CSTPCD

ISSN：

年,卷(期)：2024.9(10)