Safety and clinical efficacy of sintilimab (anti-PD-1) in pediatric patients with advanced or recurrent malignancies in a phase I study

作者全名："Que, Yi; Wang, Juan; Sun, Feifei; Wang, Shan; Zhu, Jia; Huang, Junting; Zhao, Zhenzhen; Zhang, Li; Liu, Juan; Xu, Jiaqian; Zhen, Zijun; Sun, Xiaofei; Lu, Suying; Zhang, Yizhuo"

作者地址："[Que, Yi; Wang, Juan; Sun, Feifei; Zhu, Jia; Huang, Junting; Zhang, Li; Liu, Juan; Xu, Jiaqian; Zhen, Zijun; Sun, Xiaofei; Lu, Suying; Zhang, Yizhuo] Sun Yat sen Univ, Collaborat Innovat Ctr Canc Med, Dept Pediat Oncol, State Key Lab Oncol South China,Canc Ctr, Guangzhou 510060, Peoples R China; [Wang, Shan; Zhao, Zhenzhen] Chongqing Med Univ, Childrens Hosp, Natl Clin Res Ctr ChildHealth & Disorders, Dept Surg Oncol,Minist Educ,Key Lab Child Dev & Di, Chongqing 400014, Peoples R China"

通信作者："Lu, SY; Zhang, YZ (通讯作者)，Sun Yat sen Univ, Collaborat Innovat Ctr Canc Med, Dept Pediat Oncol, State Key Lab Oncol South China,Canc Ctr, Guangzhou 510060, Peoples R China."

来源：SIGNAL TRANSDUCTION AND TARGETED THERAPY

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001082069800001

JCR分区：Q1

影响因子：40.8

年份：2023

卷号：8

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："The aim of this phase I study is to evaluate, for the first time, the safety and efficacy of sintilimab in pediatric patients diagnosed with advanced or recurrent malignancies. During the dose escalation phase, patients received a single intravenous infusion of sintilimab at varying doses of 1, 3, and 10 mg/kg. The primary endpoints included the identification of dose-limiting toxicities (DLTs) as well as the evaluation of safety and tolerance. Secondary endpoints focused on assessing objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). A total of 29 patients were enrolled, including 10 individuals diagnosed with Hodgkin lymphoma (HL) and 19 patients with various other tumor categories. Notably, diverse pathological types such as thymoma, choroid plexus carcinoma, and NK/T-cell lymphoma were also included in the study cohort. By the safety data cutoff, most adverse events were grade 1 or 2, with grade 3 or higher treatment-related adverse events (TRAE) occurring in 10% of patients. Among the 27 evaluated subjects, four achieved confirmed complete response (CR) while seven patients exhibited confirmed partial response (PR). Additionally, seven patients maintained disease (SD) during the study period. Notably, sintilimab demonstrated remarkable tolerability without DLTs and exhibited promising anti-tumor effects in pediatric HL. Whole-exome sequencing (WES) was conducted in 15 patients to assess the mutational landscape and copy number variation (CNV) status. The completion of this phase I study establishes the foundation for potential combination regimens involving sintilimab in childhood cancer treatment. The trial is registered on ClinicalTrials.gov with the identifier NCT04400851."

基金机构："We acknowledge and thank the patients and their families for their participation in this study. We also express gratitude Dr. Shirui Zheng from Innovent Biologics (Suzhou) Co., Ltd for medical assisting. This study was sponsored by The National Natural Sci [82002835]; National Natural Science Foundation of China [2022YFC2705005]; National Key Research and Development Project [202201011572]; Guangzhou Science and Technology project"

基金资助正文："We acknowledge and thank the patients and their families for their participation in this study. We also express gratitude Dr. Shirui Zheng from Innovent Biologics (Suzhou) Co., Ltd for medical assisting. This study was sponsored by The National Natural Science Foundation of China (No. 82002835), The National Key Research and Development Project (No. 2022YFC2705005) and Guangzhou Science and Technology project (No. 202201011572)."