普利单抗治疗难治性或复发性胶质瘤或脑转移瘤患者的一期剂量升级研究。

IF 3.7 Q1 CLINICAL NEUROLOGY Neuro-oncology advances Pub Date : 2024-09-30 eCollection Date: 2024-01-01 DOI:10.1093/noajnl/vdae166
Jose Carrillo, Jaya Mini Gill, Charles Redfern, Ivan Babic, Natsuko Nomura, Dhaval K Shah, Sean Carrick, Santosh Kesari
{"title":"普利单抗治疗难治性或复发性胶质瘤或脑转移瘤患者的一期剂量升级研究。","authors":"Jose Carrillo, Jaya Mini Gill, Charles Redfern, Ivan Babic, Natsuko Nomura, Dhaval K Shah, Sean Carrick, Santosh Kesari","doi":"10.1093/noajnl/vdae166","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>This phase 1 (NCT04396717) open-label, multicenter study, evaluated Pritumumab, a IgG1 monoclonal antibody, in patients with gliomas and brain metastases. The primary objective was to evaluate the safety and/or tolerability and to identify a recommended phase 2 dose (RP2D) of Pritumumab.</p><p><strong>Methods: </strong>Adult patients with recurrent gliomas or brain metastases were enrolled in the dose cohort that was open at the time of their consent. Study treatment consisted of pritumumab administered intravenously weekly on days 1, 8, 15, and 22 in 28-day cycles. Safety, pharmacokinetics (PK), pharmacodynamics (PD), and clinical activity were evaluated.</p><p><strong>Results: </strong>Fifteen patients received Pritumumab in the recurrent setting. Pritumumab was well tolerated, with no serious adverse events related to Pritumumab reported. The most common drug-related toxicities were constipation and fatigue. There were no dose-limiting toxicities observed, and a maximum tolerable dose was not reached. Thus, the maximum feasible dose and recommended phase 2 dose of Pritumumab was established at 16.2 mg/kg weekly. Out of eleven patients evaluated for efficacy, one patient (9.1%) demonstrated partial response based on response assessment in neuro-oncology criteria, and disease stabilization was seen in 3 patients (27.3%).</p><p><strong>Conclusions: </strong>Pritumumab was well tolerated with no DLTs observed up to 16.2 mg/kg weekly. Further studies are warranted to determine clinical benefit in patients.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"6 1","pages":"vdae166"},"PeriodicalIF":3.7000,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502913/pdf/","citationCount":"0","resultStr":"{\"title\":\"A phase 1 dose escalation of pritumumab in patients with refractory or recurrent gliomas or brain metastases.\",\"authors\":\"Jose Carrillo, Jaya Mini Gill, Charles Redfern, Ivan Babic, Natsuko Nomura, Dhaval K Shah, Sean Carrick, Santosh Kesari\",\"doi\":\"10.1093/noajnl/vdae166\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>This phase 1 (NCT04396717) open-label, multicenter study, evaluated Pritumumab, a IgG1 monoclonal antibody, in patients with gliomas and brain metastases. The primary objective was to evaluate the safety and/or tolerability and to identify a recommended phase 2 dose (RP2D) of Pritumumab.</p><p><strong>Methods: </strong>Adult patients with recurrent gliomas or brain metastases were enrolled in the dose cohort that was open at the time of their consent. Study treatment consisted of pritumumab administered intravenously weekly on days 1, 8, 15, and 22 in 28-day cycles. Safety, pharmacokinetics (PK), pharmacodynamics (PD), and clinical activity were evaluated.</p><p><strong>Results: </strong>Fifteen patients received Pritumumab in the recurrent setting. Pritumumab was well tolerated, with no serious adverse events related to Pritumumab reported. The most common drug-related toxicities were constipation and fatigue. There were no dose-limiting toxicities observed, and a maximum tolerable dose was not reached. Thus, the maximum feasible dose and recommended phase 2 dose of Pritumumab was established at 16.2 mg/kg weekly. Out of eleven patients evaluated for efficacy, one patient (9.1%) demonstrated partial response based on response assessment in neuro-oncology criteria, and disease stabilization was seen in 3 patients (27.3%).</p><p><strong>Conclusions: </strong>Pritumumab was well tolerated with no DLTs observed up to 16.2 mg/kg weekly. Further studies are warranted to determine clinical benefit in patients.</p>\",\"PeriodicalId\":94157,\"journal\":{\"name\":\"Neuro-oncology advances\",\"volume\":\"6 1\",\"pages\":\"vdae166\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2024-09-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502913/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neuro-oncology advances\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1093/noajnl/vdae166\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuro-oncology advances","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/noajnl/vdae166","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0

摘要

研究背景这项1期(NCT04396717)开放标签多中心研究评估了胶质瘤和脑转移患者的IgG1单克隆抗体Pritumumab。主要目的是评估普利妥单抗的安全性和/或耐受性,并确定第二阶段的推荐剂量(RP2D):方法:复发性胶质瘤或脑转移瘤成人患者在同意时被纳入剂量组群。研究治疗包括每周第1、8、15和22天静脉注射普利单抗,周期为28天。对安全性、药代动力学(PK)、药效学(PD)和临床活性进行了评估:15名患者在复发情况下接受了普妥单抗治疗。普妥珠单抗的耐受性良好,未报告与普妥珠单抗相关的严重不良事件。最常见的药物相关毒性反应是便秘和疲劳。没有观察到限制剂量的毒性反应,也没有达到最大耐受剂量。因此,普利妥单抗的最大可行剂量和第二阶段推荐剂量被确定为每周 16.2 毫克/千克。在接受疗效评估的11名患者中,有1名患者(9.1%)根据神经肿瘤学反应评估标准表现出部分反应,3名患者(27.3%)的病情趋于稳定:普利妥单抗耐受性良好,在每周16.2毫克/千克的剂量范围内未观察到DLT。结论:普立妥单抗的耐受性良好,在每周 16.2 毫克/千克的剂量范围内未出现 DLT。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
A phase 1 dose escalation of pritumumab in patients with refractory or recurrent gliomas or brain metastases.

Background: This phase 1 (NCT04396717) open-label, multicenter study, evaluated Pritumumab, a IgG1 monoclonal antibody, in patients with gliomas and brain metastases. The primary objective was to evaluate the safety and/or tolerability and to identify a recommended phase 2 dose (RP2D) of Pritumumab.

Methods: Adult patients with recurrent gliomas or brain metastases were enrolled in the dose cohort that was open at the time of their consent. Study treatment consisted of pritumumab administered intravenously weekly on days 1, 8, 15, and 22 in 28-day cycles. Safety, pharmacokinetics (PK), pharmacodynamics (PD), and clinical activity were evaluated.

Results: Fifteen patients received Pritumumab in the recurrent setting. Pritumumab was well tolerated, with no serious adverse events related to Pritumumab reported. The most common drug-related toxicities were constipation and fatigue. There were no dose-limiting toxicities observed, and a maximum tolerable dose was not reached. Thus, the maximum feasible dose and recommended phase 2 dose of Pritumumab was established at 16.2 mg/kg weekly. Out of eleven patients evaluated for efficacy, one patient (9.1%) demonstrated partial response based on response assessment in neuro-oncology criteria, and disease stabilization was seen in 3 patients (27.3%).

Conclusions: Pritumumab was well tolerated with no DLTs observed up to 16.2 mg/kg weekly. Further studies are warranted to determine clinical benefit in patients.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
6.20
自引率
0.00%
发文量
0
审稿时长
12 weeks
期刊最新文献
The landscape of immune checkpoint inhibitor clinical trials in glioblastoma: A systematic review. Cell migration simulator-based biomarkers for glioblastoma. Targeting the IDH1 R132H mutation in gliomas by CRISPR/Cas precision base editing. miR-644a is a tumor cell-intrinsic mediator of sex bias in glioblastoma. International symposium on inheritable central nervous system (CNS) cancer predisposition: A prologue.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1